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Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

Alejandro Mayer, Abimael Rodríguez, Orazio Taglialatela-Scafati and 1 more

Marine Drugs · 2013 · Review · CC BY

doi:10.3390/md11072510

Abstract

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 21, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

The current article presents a systematic review of the preclinical pharmacology of the marine natural products literature in 2009–2011, with a similar format to previous reviews, and which resulted from extensive searches of several databases, including Marinlit, PubMed, Current Contents® and Chemical Abstracts®. We have limited this review to the peer-reviewed literature that reported bioactivity or pharmacology of structurally characterized marine chemicals, and have continued to use a modification of Schmitz’s chemical classification to assign marine structures to six major chemical classes, namely, polyketides, terpenes, peptides, alkaloids, shikimates, and sugars. The preclinical antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacology of marine chemicals is presented in Table 1, with the corresponding structures shown in Figure 1. Marine compounds that affect the immune and nervous systems, as well as those with antidiabetic and anti-inflammatory effects are shown in Table 2, with their corresponding structures presented in Figure 2. Finally, marine compounds that have been demonstrated to affect a wide variety of cellular and molecular targets are exhibited in Table 3, and their structures presented in Figure 3. Several publications during 2009–2011 described extracts or as yet structurally uncharacterized marine compounds, and although they have been excluded from the current review, they certainly deserve further investigation because they report novel and interesting in vitro or in vivo preclinical pharmacology: antimicrobial and antistaphylococcal biofilm activity of three 5-kDa peptides isolated from coelomocyte effector cells of the sea urchin Paracentrotus lividus that could benefit patients with medical device-associated infections; an antibacterial polyunsaturated fatty acid, eicosapentanoic acid, isolated from extracts of the marine diatom Phaeodactylum tricornutum with activity against a range of Gram-positive and Gram-negative bacteria, including multidrug-resistant Staphyloccus aureus; potent anticoagulant activity of sulfated polysaccharides isolated from the Brazilian brown seaweed Dictyota cervicornis, which was close to that of clinically used low molecular weight heparin; potent anticoagulant activity of a sulfated polysaccharide isolated from the Chinese green seaweed Monostroma latissimum by a mechanism involving thrombin inhibition in the presence of heparin cofactor II; in vitro antileishmanial activity of dichloromethane extracts of a Tunisian sponge Sarcotragus sp., which demonstrated concomitant morphological alterations of Leishmania major promastigotes in vitro; in vivo and in vitro antifilarial activity of the marine sponge Haliclona exigua extracts against adult nematode Brugia malayi, a parasite that may cause lymphatic filariasis; significant nontoxic and anti-herpes simplex virus HSV-1 and HSV-2 activity in sulfated polysaccharide extracts isolated from four species of red and brown marine algae from New Zealand; anti-herpes simplex virus HSV-1 activity in high molecular weight exopolysaccharides purified from the French marine sponge Celtodoryx girardae and its symbiotic bacteria; anti-inflammatory activity of the crude extracts and fractions of the Mediterranean sponge Spongia officinalis in the in vivo rat carrageenan-induced paw edema assay; in vivo anti-inflammatory activity in polyphenolic extracts from the red alga Laurencia undulata resulting in significant inhibition of asthmatic reactions; in vitro anti-inflammatory effect in an ethanolic extract from the brown alga Ishige okamurae via inhibition of NF-κB transcription factor; induction of oxidative death in a human glioma cell line through a caspase-9 apoptotic pathway by extracts from the marine sponge Polymastia janeirensis; apoptotic activity in extracts from the marine diatom Cocconeis scutellum associated with activation of caspases-8 and -3 in human breast cancer lines; human neutrophil anti-elastase activity of purified sulfated polysaccharides from the red alga Delesseria sanguinea; high antioxidant activity in methanolic extracts of the Korean red alga Polysiphonia morrowii that protected against hydroxyl radical-induced DNA damage in vitro; antioxidant activity in phenolic compounds from the marine alga Halimeda monile that protected against chemically induced rat liver injury in vivo; significant antioxidant properties of polysaccharides from a marine fungus Penicillium sp. F23-2 against superoxide and hydroxyl radicals; in vitro antioxidant activities of acetylated, phosphorylated and benzoylated derivatives of the marine red alga Porphyra haitanensis phorphyran; acceleration of skin wound healing by amino acids isolated from the mollusc Rapana venosa suggesting a possible therapeutic use in skin burns; neuroprotective effects in extracts of the South Indian green seaweed Ulva reticulata that inhibited both acetyl-and butyryl-cholinesterases, and was comparable to agents currently approved for Alzheimer’s disease treatment.

2. Marine Compounds with Antibacterial, Antifungal, Antiprotozoal, Antituberculosis, and Antiviral Activities

Table 1 presents the 2009–2011 preclinical pharmacological research on the antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities of the marine natural products (1–102) shown in Figure 1.

2.1. Antibacterial Activity

During 2009–2011, 35 studies reported antibacterial marine natural products isolated from a diverse group of marine bacteria, ascidians, bryozoans, sponges, soft corals and algae, a persistent effort on which we have reported previously, and which continues to contribute to the global health challenge posed by drug-resistant bacteria.

Only four papers reported molecular mechanism of action studies with marine antimicrobial compounds. Plaza and colleagues investigated bisdiarylbutene macrocycle chrysophaentin A (1) from the chrysophyte alga Chrysophaeum taylori that potently inhibited Gram positive methicillin-resistant Staphylococus aureus (minimum inhibitory concentration [MIC]50 = 1.5 μg/mL) and vancomycin-resistant Enterococcus faecium (MIC50 = 2.9 μg/mL) by binding and inhibiting GTPase activity of the essential bacterial cell division protein FtsZ. Two studies contributed to the ongoing search of quorum sensing antagonists as potentially novel antimicrobial drugs: Teasdale and colleagues extended the pharmacology of two previously described phenethylamide metabolites isolated from a marine Gram positive Halobacillus salinus strain. One of these compounds, 3-methyl-N-(2′-phenylethyl)-butyramide (2) interfered with quorum sensing-regulated activities (e.g., bioluminescence inhibition IC50 = 9 μg/mL) in several Gram negative species. Kwan and colleagues isolated a small cyclopropane-containing fatty acid, lyngbyoic acid (3) from the marine cyanobacterium Lyngbya cf. majuscula that affected both quorum sensing pathways (acylhomoserine lactone receptor LAsR (IC50 = 100 µM) as well as gene expression in Pseudomonas aeruginosa. Jeon and colleagues extended the pharmacology of the pyrroloiminoquinone alkaloids of the discorhabdin class isolated from the Korean marine sponge Sceptrella sp.. A new alkaloid (−)-discorhabdin Z (4), possessing a unique hemiaminal group, inhibited sortase A (IC50 = 6.5 μM), a bacterial transpeptidase that has been shown to covalently attach proteins to the bacterial cell wall and has become an important antimicrobial target.

As shown in Table 1 and Figure 1, several marine chemicals, some of them novel, were reported to exhibit antibacterial activity with MICs < 10 μg/mL or 10 μM against several bacterial strains, although no mechanism of action studies were reported for these compounds: a new alkaloid agelasine D (5) isolated from the marine sponge Agelas nakamurai collected in Bali, Indonesia; the maleimide mixture aqabamycin E (6) discovered in a marine Vibrio sp. growing on the surface of the Red Sea soft coral Sinularia polydactyla; two new cyclodepsipeptides, bacillistatins 1 and 2 (7,8) purified from cultures of the Chilean bacterium Bacillus silvestris obtained from a crab; new diterpene–benzoate macrolides bromophycolides J–Q (9–14) from the Fijian red alga Callophycus serratus; a novel benzoxazole antibiotic caboxamycin (15) produced by the deep-sea Streptomyces sp. NTK 937 isolated in the Canary Basin; a brominated polyphenyl ether crossbyanol B (16) isolated from the Hawai’ian marine cyanobacterium Leptolyngbya crossbyana; three novel pyridoacridine alkaloids (17–19) characterized from the Mediterranean ascidian Cystodytes dellechiajei; the previously-described Fijian Cymbastela hooperi diterpene isonitrile (20) recently re-evaluated; a novel alkaloid eusynstyelamide F (21), isolated from an Arctic bryozoan Tegella cf. spitzbergensis; a novel cembranoid diterpene, knightol (22), found in the Colombian gorgonian octocoral Eunicea knighti; the novel antibiotic MC21-B (23) produced by the marine bacterium Pseudoalteromonas phenolica O-BC-30T; a novel long-chain 2H-azirine 2-carboxylic acid, motualevic acid F (24), described from a Fijian marine sponge Siliquariaspongia sp.; the thiopeptide TP-1161 (25), identified in a Norwegian marine-sediment derived Gram positive Nocardiopsis sp. bacterium; two novel α-pyrone macrolides neurymenolides A and B (26, 27) isolated from the Fijian red alga Neurymenia fraxinifolia; two polybrominated metabolites (28, 29) from a Hawai’ian marine bacterium Pseudoalteromonas sp. found on the surface of a nudibranch; pseudopterosin U (30) discovered in the Caribbean octocoral Pseudopterogorgia elisabethae; 5-bromo-8-methoxy-1-methyl-β-carboline (31), an alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa; a new rifamycin antibiotic, salinisporamycin (32), purified from a culture of the Micronesian marine actinomycete Salinispora arenicora YM23-082; a novel bioactive alkaloid, synoxazolidinone A (33), discovered in the sub-Arctic Norwegian ascidian Synoicum pulmonaria.

Furthermore, during 2009–2011, several marine natural products were noted to have MIC or IC50 ranging from 10 to 50 μg/mL, or 10–50 μM, respectively, and thus because of their lower antibacterial potency were excluded from Table 1 and Figure 1: a novel casbane diterpenoid 10-hydroxydepressin (MIC = 17 μg/mL) from the Hainan soft coral Sinularia depressa; a novel guai-2-en-10α-methyl methanoate from the marine alga Ulva fasciata (MIC = 25–30 μg/mL); a novel gymnochrome F (MIC = 12.5 μg/mL) from the deep-water crinoid Holopus rangii; several novel fatty acids, ieodomycins (MIC = 32–64 μg/mL), from a marine Bacillus sp.; a novel sulfated sesterterpene alkaloid 19-oxofasciospongine A from a marine sponge Fasciospongia sp. (MIC = 20 μg/disk); a novel phenalenone derivative (MIC = 24 μM) from the marine-derived fungus Coniothyrium cereale; a novel 4,4′-oxybis[3-phenylpropionic acid] from the marine bacterium Bacillus licheniformis (IC50 = 50 μg/disk); a novel sargafuran (MIC = 15 μg/mL) from the marine brown alga Sargassum macrocarpum; a novel tetracyclic brominated diterpene (MIC = 32 μg/mL) from the red alga Sphaerococcus coronopifolius; and a new bromotyrosine alkaloid tyrokeradine B (MIC = 25 μg/mL) from a Verongid marine sponge.

Finally, during 2009–2011, several publications described novel marine antimicrobial peptides: centrocins 1 and 2, two novel dimeric peptides (MIC = 1.3–2.5 μM) from the Norwegian green sea urchin Strongylocentrotus droebachiensis; halocyntin and papillosin, two new peptides (MIC = 0.75–25 μM) isolated from hemocytes of the Mediterranean ascidian Halocynthia papillosa; and hyastatin, a glycine-rich multi-domain peptide (MIC = 0.4–12.5 μM) from hemocytes of the Norwegian spider crab Hyas araneus.

2.2. Antifungal Activity

Ten studies during 2009–2011 reported on the antifungal activity of several novel marine natural products isolated from marine bacteria, sponges and bryozoa, a slight decrease from our last review, and previous reviews of this series.

As shown in Table 1, only two reports described antifungal marine chemicals with novel mechanisms of action. DiGirolamo and colleagues identified two new sulfated sterols, geodisterol-3-O-sulfate (34) and 29-demethylgeodisterol-3-O-sulfate (35), in a marine sponge Topsentia sp., which enhanced the activity of the clinically used triazole antifungal agent fluconazole by reversing efflux pump-mediated fluconazole resistance in Candida albicans. Nishimura and colleagues extended the pharmacology of the bicyclic antifungal dodecapeptide theonellamide F (36) previously isolated from a sponge Theonella sp.. Chemical-genomic profiling analysis together with detailed subcellular localization studies determined that the antifungal theonellamides represent a new class of sterol-binding molecules that induce membrane damage and activate Rho1-mediated 1,3-β-d-glucan synthesis.

Furthermore, as shown in Table 1 and Figure 1 several marine natural products showed significant antifungal activity (i.e., MICs that were either less than 10 μg/mL, 10 μM, or 10 μg/disk), although no mechanism of action studies were reported in the published articles: the antibacterial alkaloid 5-bromo-8-methoxy-1-methyl-β-carboline (31) isolated from the New Zealand marine bryozoan Pterocella vesiculosa; a novel linear tetrapeptide citronamide A (37) from the Australian sponge Citronia astra; two holostan-type triterpenoid glycosides, marmoratoside A (38) and 17α-hydroxy impatienside A (39), from the Chinese sea cucumber Bohadschia marmorata; the polyketide saadamycin (40) from an endophytic Streptomyces sp. strain Hedaya 48 isolated from the Egyptian sponge Aplysina fistularis, and two novel depsipeptides, theopapuamides B & C (41,42), isolated from the Indonesian marine sponge Siliquariaspongia mirabilis. Future mechanism of action studies with these potent compounds will hopefully characterize their molecular pharmacology.

Finally, several novel structurally-characterized marine molecules demonstrated MICs or IC50s greater than 10 μg/mL or 10 μM, and therefore, because of the reported weaker antifungal activity, have been excluded from Table 1 and Figure 1: the maleimide mixture aqabamycin E (6) (MIC = 50 μg/mL); the novel antibacterial alkaloid synoxazolidinone A (33) (MIC = 12.5 μg/mL), and the new bromotyrosine tyrokeradine B (MIC = 12.5 μg/mL).

These marine compounds may provide novel pharmacological leads thus contributing to the global search for clinically useful antifungal agents.

2.3. Antiprotozoal and Antituberculosis Activity

As shown in Table 1, during 2009–2011 thirty two studies contributed to novel findings on the antiprotozoal and antituberculosis pharmacology of structurally characterized marine natural products, a considerable increase from previous 1998–2008 reviews.

Malaria, which is caused by protozoa from the genus Plasmodium (P. falciparum, P. ovale, P. vivax and P. malariae), affects millions of people worldwide. Contributing to the global search for novel antimalarial drugs, and as presented in Table 1, twenty six novel marine molecules were shown during 2009–2011 to possess antimalarial activity, although mechanism of action studies were reported for only two compounds. Taglialatela-Scafati and colleagues extended the molecular pharmacology of plakortin (43), isolated from the Caribbean marine sponge Plakortis simplex, which potently inhibited CQ-resistant strains of Plasmodium falciparum. Plakortin was observed to give rise to toxic carbon radicals which were ultimately “responsible for subsequent reactions leading to Plasmodium death”. Lebouvier and colleagues reported that the homogentisic acid derivative 44 from a Vanuatu marine sponge Pseudoceratina sp. was moderately active in vitro against FcB1 P. falciparum strain, while concomitantly inhibiting the specific protein kinase pfnek-1 of the parasite (IC50 = 1.8 μM). Thus, compound 44 “could serve as a model for the development of new pfnek-1 inhibitors”.

Potent (<2 µM) to moderate (>2–10 µM) antimalarial activity was reported for 24 marine natural products. Laville and colleagues isolated several novel guanidine batzelladine alkaloids (45–48) from the Caribbean marine sponge Monanchora arbuscula, which showed potent antimalarial activity against the human malaria parasite Plasmodium falciparum strain FcB1 (IC50 = 0.2–0.9 μM). Lane and colleagues characterized new diterpene–benzoate macrolides bromophycolides J, M, N, O, P and Q (9–14) from the Fijian red alga Callophycus serratus with potent antimalarial activity against P. falciparum (IC50 = 0.5–2.9 μM). Furthermore, Lin and colleagues isolated bromophycolides R, S and U (49–51) from the same Fijian red alga Callophycus serratus with potent antimalarial activity (IC50 = 0.9–2.1 μM) against P. falciparum. Davis and colleagues identified a novel β-carboline alkaloid, (+)-7-bromotrypargine (52), from an Australian marine sponge Ancorina sp. with moderate antimalarial activity (IC50 = 3.5–5.4 μM) against both chloroquine resistant (Dd2) and chloroquine-sensistive (3D7) P. falciparum strains. Wright and colleagues reported a diterpene formamide (53) from the tropical marine sponge Cyambastela hooperi that had moderate to potent activity (IC50 = 4.3 ng/mL and 0.5 μg/mL) against P. falciparum strains FCR3F86, W2 and D6. Jiménez-Romero and colleagues contributed a novel five-membered-ring polyketide endoperoxide epiplakinidioic acid (54) from the Puerto Rican sponge Plakortis halichondrioides that was potent (IC50 = 0.3 μg/mL) against the W2 chloroquinone-resistant strain of P. falciparum. Linington and colleagues purified a novel linear peptide, gallinamide A (55), from a cyanobacterium Schizothrix sp. with moderate antimalarial activity (IC50 = 8.4 μM) against chloroquine-resistant P. falciparum, yet with a structure that might become an “attractive foundation for further SAR investigations”. Ueoka and colleagues investigated a new polyketide, gracilioether B (56), from the Japanese marine sponge Agelas gracilis that was potent (IC50 = 0.5 µg/mL) against P. falciparum strain ItG. Wattanapiromsakul and colleagues isolated a new isocyanoditerpene, 8-isocyanoamphilecta-11 (20), 15-diene (57), from a Thai sponge Ciocalapata sp. with potent antimalarial activity (IC50 = 0.98 μM) against P. falciparum chloroquine-resistant strain K1. Tripathi and colleagues found two new cyclic depsipeptides, lagunamides A (58) and B (59), from the Singaporean marine cyanobacterium Lyngbya majuscula with potent antimalarial activity (IC50 = 0.19–0.91 μM) against the drug-sensitive NF54 P. falciparum strain. Fattorusso and colleagues discovered that a new endoperoxyketal, manadoperoxide C (60), from the Indonesian sponge Plakortis cf. simplex, had moderate in vitro antiplasmodial activity (IC50 = 2.3 μM) against the W2 chloroquinone-resistant strain of P. falciparum as well as provided further insight into “the structure activity relationships of simple 1,2-dioxane antimalarials”. Yamada and colleagues identified a novel alkaloid 3,4-dihydro-manzamine J N-oxide (61) from an Okinawan marine sponge Amphimedon sp. with potent in vitro antiplasmodial activity (IC50 = 0.58 μg/mL) against the K1 strain of P. falciparum. Wei and colleagues extracted a new tetracyclic bis-piperidine alkaloid, neopetrosiamine A (62), from the Puerto Rican marine sponge Neopetrosia proxima with moderate antiplasmodial activity (IC50 = 2.3 μM) against P. falciparum and low concomitant cytotoxicity to Vero cells. Yang and colleagues extended the pharmacology of the known bromotyrosine alkaloid psammaplysin F (63) from an Australian marine sponge Hyattella sp. by reporting potent inhibition (IC50 = 0.87–1.4 μM) of P. falciparum 3D7 and Dd2 strains.

Eighteen marine compounds were reported to possess activity against other protozoa thus contributing to the ongoing global search for novel agents for the so-called neglected diseases, namely leishmaniasis (caused by several species of the genus Leishmania), amebiasis, trichomoniasis, African sleeping sickness (caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense) and American sleeping sickness or Chagas disease (caused by Trypanosoma cruzi). Dos Santos and colleagues reported that a 4-acetoxydolastane diterpene (64) isolated from the Brazilian brown alga Canistrocarpus cervicornis dose-dependently inhibited promastigote, axenic amastigote and intracellular amastigote forms of Leishmania amazonensis (IC50 = 2.0, 12.0 and 4.0 μg/mL, respectively) by extensive mitochondrial damage and lipid peroxidation.

As shown in Table 1 and Figure 1, several marine natural products were characterized to exhibit antiprotozoal activity, although the mechanism of action of these compounds remains undetermined. Vik and colleagues completed a comprehensive screening of agelasine terpene analogs from a marine sponge Agelas sp. and reported that four agelasine analogs (65–68) potently inhibited Leishmania infantum, T. brucei brucei and T. cruzi (IC50 = 0.093–0.11; 0.11–0.23; 0.11–0.43 μg/mL, respectively) with low concomitant cytotoxicity, suggesting they could become novel leads for design of “potent and selective drugs”. Sanchez and colleagues found two novel linear lipopeptides, almiramides B and C (69,70), from the marine cyanobacterium Lyngbya majuscula that inhibited the protozoan parasite Leishmania donovani (IC50 = 1.9–2.4 μM) with minimal cytotoxicity towards Vero cells (IC50 = 33.1–52.3 μM). Davis and colleagues investigated a new brominated alkaloid, convolutamine I (71), from the bryozoan Amathia tortusa that was highly active towards the parasite Trypanosoma brucei brucei (IC50 = 1.1 μM), yet presenting low cytotoxicity in human embryonic kidney cells (IC50 = 22.0 μM). Scala and colleagues completed the first antiprotozoal screening of marine bromopyrrole alkaloids isolated from the marine sponges Axinella verrucosa and Agelas dispar and determined that longamide B (72) and dibromopalau’amine (73) inhibited Trypanosoma brucei rhodesiense (IC50 = 1.53 & 0.46 μg/mL, respectively), and Leishmania donovani (IC50 = 3.85 & 1.09 μg/mL, respectively), with low cytotoxicity. Cantillo-Ciau and colleagues isolated two known and one novel sulfoquinovosyl diacylglycerols (74–76) from the Mexican tropical brown alga Lobophora variegata with high antiprotozoal activity against E. histolytica (IC50 = 3.9 μg/mL) and moderate activity towards Trichomonas vaginalis trophozoites (IC50 = 8.0 μg/mL), and with a good selectivity index (SI > 10). Yamada and colleagues characterized a novel alkaloid 3,4-dihydro-manzamine J N-oxide (61) from an Okinawan marine sponge Amphimedon sp. which displayed moderate in vitro activity against Trypanosoma brucei brucei (IC50 = 0.27 μg/mL). Rubio and colleagues evaluated several known peroxiterpenes as well as a novel (+)-muqubilone B (77) from the Papua New Guinea marine sponge Diacarnus bismarckensis shown to inhibit Trypanosoma brucei brucei (IC50 = 2 μg/mL), concluding that these marine chemicals could become “therapeutic leads” against T. brucei. Ma and colleagues identified novel highly oxidized steroids norselic acids A–E (78–82) isolated from an Antarctic marine sponge Crella sp. which moderately inhibited Leishmania sp. (IC50 = 2.0–3.6 μM). Regalado and colleagues reinvestigated the Caribbean sponge Pandaros acanthifolium and discovered that among several new steroidal glycosides, both pandaroside G (83) and pandaroside G methyl ester (84) potently inhibited the growth of Trypanosoma brucei rhodesiense (IC50 = 0.8 and 0.038 μM, respectively), and Leishmania donovani (IC50 = 1.3 and 0.051 μM, respectively) but with rather high concomitant cytotoxicity. Feng and colleagues isolated a novel cyclic polyketide peroxide, 11,12-didehydro-13-oxo-plakortide Q (85), from an Australian marine sponge Plakortis sp. with significant activity (IC50 = 0.049 μM) against Trypanosoma brucei brucei. Pimentel-Elardo and colleagues reported the isolation of the known cyclic depsipeptide valinomycin (86) from marine Streptomyces sp. strains associated with several Croatian marine sponges, and observed significant activity against both Trypanosoma brucei brucei (IC50 = 0.0032 μM) and Leishmania major (IC50 < 0.11 μM).

As shown in Table 1, four novel marine natural products contributed to the global search for novel antituberculosis agents, a decrease from our previous reviews.

Vicente and colleagues extended the pharmacology of the known compound hymenidin (87) from the Puerto Rican marine sponge Prosuberites laughlini by demonstrating its antimycobacterial activity (MIC = 6.1 μg/mL) against M. tuberculosis H37Rv. Pruksakorn and colleagues isolated three new aminolipopeptides, trichoderins A (88), A1 (89) and B (90) from a marine sponge-derived fungus Trichoderma sp. that potently inhibited (MIC = 0.02–2.0 μg/mL) the M. tuberculosis strain H37Rv under both aerobic and dormancy-inducing conditions. Wei and colleagues isolated tetracyclic bis-piperidine alkaloid neopetrosiamine A (62) from the Puerto Rican marine sponge Neopetrosia proxima which inhibited growth (MIC = 7.5 μg/mL) of the pathogenic strain Mycobacterium tuberculosis H37Rv. Although all of these studies demonstrate that marine alkaloids and peptides may potentially become novel antituberculosis leads, further studies are required to determine the molecular pharmacology of these compounds.

2.4. Antiviral Activity

As shown in Table 1, three reports were published during 2009–2011 on the antiviral pharmacology of novel marine natural products against human cytomegalovirus and herpes simplex virus. Cheng and colleagues purified two new diterpenoids, gyrosanols A and B (91,92), and two novel cembranoids, lobophynin C and ehrenberoxide B (93,94), from the Taiwanese soft corals Sinularia capillosa and Sarcophyton ehrenbergi, respectively, which inhibited the herpes virus-5 or cytomegalovirus (HCMV) (IC50 = 2.6–5.8 μM), an interesting preclinical contribution because HCMV infections may be life-threatening in immunocompromised patients. Palem and colleagues extended the pharmacology of the known β-carboline alkaloid manzamine A (95), isolated from an Indo-Pacific sponge Acanthostrongylophora sp., by demonstrating the compound inhibited HSV-1 infection (apparent IC50 = 1 μM) in rabbit corneal cells by affecting viral immediate-early gene transcription.

Three articles reported preclinical pharmacology of marine compounds active against the human immunodeficiency virus type-1 (HIV-1), the causative agent of the acquired immunodeficiency disease syndrome (AIDS), a decrease from our previous review. Ding and colleagues investigated the novel pentacyclic indolosesquiterpene xiamycin (96) isolated from the Streptomyces sp. GT2002/1503 bacterium and demonstrated selective inhibition against macrophage and T cell β-chemokine receptor CCR5 (5) tropic HIV-infection (estimated IC50 = 7.2 μg/mL), with no effect against α-chemokine receptor CXCR4 (X4) tropic HIV. Fan and colleagues isolated several DOPA-derived pyrrole alkaloids, baculiferins I, J, L and M (97–100), from the Chinese marine sponge Iotrochota baculifera, which were found to be potent inhibitors of HIV-1 IIIB (IC50 = 0.2–7.0 μM) by binding to the HIV target proteins Vif, APOBEC3G, and gp41 in an as yet undetermined mechanism. Plaza and colleagues isolated several new cyclic depsipeptides from the Indonesian marine sponge Siliquariaspongia mirabilis including celebesides A and C (101–102), which inhibited HIV-1 in an infectivity assay (IC50 = 1.9 ± 0.4 μg/mL), thus correlating the anti-HIV activity of these compounds with the presence of phosphoserine.

3. Marine Compounds with Antidiabetic and Anti-Inflammatory Activity, and Affecting the Immune and Nervous System

Table 2 presents the preclinical pharmacology of marine chemicals (103–162) which demonstrated antidiabetic and anti-inflammatory activity, as well as affected the immune and nervous system, and whose structures are shown in Figure 2.

3.1. Antidiabetic Activity

Heo and colleagues extended the pharmacology of diphlorethohydroxycarmalol [DPHC] (103), previously isolated from the marine brown alga Ishige okamurae, by showing that DPHC alleviated postprandial hyperglycemia in diabetic mice by potent inhibition of both α-glucosidase and α-amylase enzymes (IC50 = 0.16 and 0.53 nM, respectively) suggesting a possible use of DPHC “as a nutraceutical or functional food for diabetes”. Li and colleagues evaluated the known sesquiterpene dysidine (104) from the Hainan marine sponge Dysidea villosa, and revealed that it activated the insulin pathway by inhibition of human protein phosphatase 1B (IC50 = 6.70 µM), a well characterized drug target for type-II diabetes and obesity treatment, as well as glucose uptake and glucose transporter 4 translocation in vitro.

3.2. Anti-Inflammatory Activity

There was a remarkable increase in marine anti-inflammatory pharmacology research during 2009–2011. The molecular mechanism of action of several marine natural products, which were shown in preclinical pharmacological studies to target neutrophils and macrophages both in vitro and in vivo, was reported in several publications. Asolkar and colleagues described two new cyclohexadepsipeptides arenamides A and B (105,106), isolated from the Fijian bacterium Salinispora arenicola, that inhibited LPS-induced murine macrophage RAW 264.7 cells PGE2 and NO production in vitro, by affecting NFκB signaling activity (IC50 = 3.7 and 1.7 μM, respectively), thus highlighting their “anti-inflammatory characteristics”. Three publications yielded potentially novel compounds targeting proinflammatory mediators released by activated brain microglia, a macrophage involved in neuroinflammation and neurodegeneration: Youssef and colleagues described a new steroid callysterol (107) from the Red Sea sponge Callyspongia siphonella, which potently inhibited rat hind paw edema with an activity close to cortisone, and also reduced TXB2 release from LPS-activated rat brain microglia (apparent IC50 > 10 μM). Jean and colleagues observed that the sesquiterpene capnellene (108) isolated from the Indonesian soft coral Capnella imbricate, attenuated expression of inducible cyclooxygenase-2 both in activated microglia in vitro and in vivo, suggesting it might contribute to “the search for new therapeutic agents for treatment of neuroinflammatory diseases”. Shi and colleagues isolated a new terpene, elisabethin H (109) from the Caribbean gorgonian octocoral Pseudopterogorgia elisabethae, which significantly inhibited superoxide anion (O2–) generation from E. coli LPS activated rat neonatal microglia in vitro (IC50 = 7 μM). Li and colleagues reported that the floridosides (110,111), isolated from the South Korean marine red alga Laurencia undulata, possessed significant antioxidant capacity and inhibited the proinflammatory matrix metalloproteinases MMP-2 and MMP-9, thus suggesting they might be candidates for further development as natural marine antioxidants. Three publications investigated inhibition of pro-inflammatory mediators released by activated macrophage cell lines: Malloy and colleagues reported that the lipopeptide malyngamide 2 (112) from the Papua New Guinea marine cyanobacterium Lyngbya sordida inhibited nitric oxide production in LPS-primed RAW 264.7 macrophage cells (IC50 = 8.0 μM). In a detailed mechanistic study Villa and colleagues investigated the lipopeptide malyngamide F (113) from the marine cyanobacterium Lyngbya majuscula showing that it inhibited nitric oxide production in LPS-primed RAW 264.7 macrophage cells (IC50 = 7.1 μM) by selectively inhibiting the MyD88-dependent pathway of TLR4 and 9, thus potentially becoming a “useful tool” in cellular biology. Kim and colleagues extended previous studies with the phlorotannin phlorofucofuroeckol A (PFF-A) (114), isolated from the Korean brown alga Ecklonia stolonifera, by demonstrating its antioxidant activity was of similar potency to vitamin C, and that it inhibited nitric oxide and PGE2 production (apparent IC50 = 5–10 μM) by downregulation of iNOS and COX-2 protein expression in LPS-primed RAW 264.7 macrophage cells. Using an in vivo rat colitis model, Belmiro and colleagues provided a detailed molecular characterization of the anti-inflammatory properties of a dermatan sulfate (115), analog of mammalian heparin, purified from the Brazilian ascidian Styela plicata, which at 8 mg/kg per day significantly decreased lymphocyte and macrophage recruitment as well as TNF-α, TGF-β, and VEGF production in the inflamed rat colon. Hanif and colleagues reported that the highly hydroxylated long-chain sulfate symbiopolyol (116), isolated from a symbiotic dinoflagellate of the jellyfish Mastigias papua significantly inhibited (K50 = 6.6 μM) the expression of the inducible adhesion vascular cell adhesion molecule-1 which binds to leukocytes present in early stages of inflammation, and thus might become a “potential anti-inflammatory agent”. Costantino and colleagues reported that tedanol (117), a new brominated and sulfated pimarane diterpene isolated from the Caribbean sponge Tedania ignis, significantly reduced both the acute and subchronic phases of carrageenan-induced inflammation at 1 mg/kg with concomitant inhibition of both COX-2, iNOS expression and cellular infiltration.

As shown in Table 2 and in contrast to the marine anti-inflammatory compounds previously discussed, while an anti-inflammatory activity and IC50 were reported, the molecular mechanism of action remained undetermined for the following marine compounds: carijoside A (118); chabrosterol (119); coscinolactams (120–122); durumhemiketalolide C (123); durumolide F (124); gyrosanolides B and C (125,126); klysimplexin sulfoxide C (127); L. crassum diterpenes (128,129); perthamides C and D (130,131); rossinones A and B (132,133); nebrosteroid I (134); sarcoehrenosides A and B (135,136); sarcocrassocolides A & B (137,138); simplexin E (139); and terpioside B (140).

3.3. Marine Compounds with Activity on the Immune System

In 2009–2011, immune system pharmacology of marine compounds showed a considerable decrease from our previous review.

Kwan and colleagues isolated the linear peptides grassystatins A–C (141–143) from a marine cyanobacterium identified as Lyngbya cf. confervoides, demonstrating that the compounds selectively inhibited aspartic protease cathepsin E (IC50 = 0.3–0.8 nM) versus cathepsin D, as well as antigen-stimulated T cell proliferation, with a concomitant reduction of IL-17 and interferon γ. Takei and colleagues reported that the known compounds callyspongidiol (144) and 14,15-dihydrosiphonodiol (145), isolated from a marine sponge Callyspongia sp., activated both functional and phenotypic maturation of human monocyte-derived dendritic cells, as well as higher interleukin-10 production by T cells, thus revealing potential use in autoimmune diseases and cancer. Shim and colleagues observed that the phloroglucinol derivative phlorofucofuroeckol A (PFF-A) (114), purified from the Korean marine seaweed Ecklonia stolonifera, reduced the expression of the human basophil FcεR1 receptor (apparent IC50 = 25 µM), as well as intracellular [Ca2+]i and histamine release, findings which may be relevant for regulation of IgE-mediated allergic reactions. Strangman and colleagues discovered novel splenocin B (146) isolated from the marine bacterium Streptomyces species strain CNQ431 that displayed potent inhibition of murine splenocyte-derived TH2 cytokines interleukin 5 and 13 (IC50 = 1.6–1.8 nM), thus contributing to the development of a “splenocin-derived drug” for allergic inflammation. Dai and colleagues isolated a water soluble polysaccharide HCLPS-1 (147) from the Chinese pearl-producing mollusc Hyriopsis cumingii Lea, which stimulated murine spleen lymphocyte proliferation in vitro and in vivo in a concentration-dependent manner (apparent IC50 less than 20 mg/kg), suggesting HCLPS-1 might become a “potential natural immunomodulator” upon further pharmacological study. Orsi and colleagues contributed to the immunopharmacology of the sulfated dinoflagellate polyether yessotoxin (148), by demonstrating that it decreased macrophage phagocytic activity against the fungus Candida albicans (apparent IC50 = 1 nM), affected the cytoskeleton by inducing F-actin re-organization, and enhanced release of the cytokine TNF-α and chemokines MIP-1α and MIP-2.

3.4. Marine Compounds Affecting the Nervous System

As shown in Table 2, the nervous system pharmacology of marine natural products in 2009–2011 involved some areas of neuropharmacology, namely neuronal neurite retraction, neurotransmission inhibition, neuronal Ca2+ oscillations and free radical inhibition.

Marine natural products have previously been reported to affect neuritogenesis, a process required by neurons to respond to the extracellular environment to form synaptic connections. Inutsuka and colleagues contributed novel molecular studies on the effect of calyculin A (149) on neurons, demonstrating that rapid rat hippocampal neuron neurite retraction (apparent IC50 = 100 mM) induced by the toxin was dependent on actin filament polymerization or myosin II motor, yet independent of the microtubule polymerization status, and perhaps resulted from dephosphorylation of myosin light chain kinase. Sakurada and colleagues reported that the novel Palauan sponge Cribrochalina olemda purine (150), which elicited convulsions upon intracerebroventricular injections in mice (4 nM/mouse), inhibited GABAergic transmission in hippocampal neurons. Noteworthy was the author’s observation that this marine purine was “closely related in structure to endogenous neurosignaling molecules and commonly used CNS stimulants”.

As shown in Table 2, two marine compounds (151,152) identified as part of a drug discovery screening program, were shown to inhibit neuronal Ca2+ oscillations, a network phenomenon that appears to depend on voltage-gated sodium channel activation. Choi and colleagues reported that a cyclic depsipeptide hoiamide B (151), isolated from a Papua New Guinean cyanobacteria assemblage of Symploca sp. and Oscillatoria cf. sp., stimulated sodium influx (IC50 = 3.9 µM) in murine neuronal cells in vitro by putative activation of site 2 on the sodium channel, while suppressing spontaneous Ca2+ (IC50 = 79.8 nM) with greater potency, thus revealing that hoiamide B may have more than one molecular target. Pereira and colleagues contributed a novel marine macrolide palmyrolide A (152) isolated from Northern Pacific Palmyra Atoll cyanobacteria assemblages of Leptolyngbya cf. and Oscillatoria sp. that inhibited both sodium influx (IC50 = 5.2 µM) in mouse neuroblastoma cells and spontaneous Ca2+ oscillations (IC50 = 3.7 µM) in primary cultures of murine cerebrocortical neurons, “making it an intriguing candidate for further pharmacological exploration”. Zhao and colleagues reported that the known compound xyloketal B (153), isolated from the marine mangrove fungus Xylaria sp., inhibited ischemia-induced PC12 cell injury (IC50 = 100 µM) by a neuroprotective mechanism involving free radical scavenging and reduction of mitochondrial membrane potential and superoxide generation, suggesting further development for effective stroke therapy.

Finally, and as presented in Table 2, during 2009–2011, several other marine compounds were reported to affect the nervous system by demonstrating pharmacological activity on Ca2+ oscillations, several receptors, and neuronal nitric oxide synthase, yet the mechanism of action of these compounds remained undetermined: alotamide A (154), (−)-dibromophakellin (155), dysideamine (156), ircinialactams (157,158), eusynstyelamides B and C (159,160), nanolobatolide (161), and pulicatin A (162).

4. Marine Compounds with Miscellaneous Mechanisms of Action

Table 3 presents the 2009–2011 preclinical pharmacology of 68 marine compounds (163–226) with miscellaneous mechanisms of action, with their respective structures shown in Figure 3. Because additional in vitro and in vivo pharmacological data for these compounds remained unpublished, assignment of these marine compounds to a particular drug class was not possible.

As shown in Table 3, the peer-reviewed literature reported a pharmacological activity, an IC50, and a molecular mechanism of action for 21 marine natural products: bisebromoamide (163); botryllamides I and J (164,165); dysidine (104); Ecklonia cava phlorotannins (166,167); fucophlorethols (168,169); gonad-stimulating substance (GSS) (170); halichlorine (171); hoiamide A (172); hypochromins A and B (173,174); mycothiazole (175); Mycale sp. pyrroles (176,177); neocomplanines A and B (178,179); pateamine A (180); polytheonamide B (181); and zampanolide (182).

In contrast, although a pharmacological activity was described, and an IC50 for inhibition of an enzyme or receptor determined, detailed molecular mechanism of action studies were unavailable at the time of publication for the following 47 marine compounds included in Table 3: alotaketals A and B (183,184); aquastatin A (185); australin E (186); lyngbyastatins 9 & 10 (187,188); brunsvicamides A, B and C (189–191); carteriosulfonic acids A, B and C (192–194); Carteriospongia foliascens sesterterpenoids (195,196); clavatadines D and E (197,198); fibrosterol sulfates A and B (199,200); gracilin L (201); grassystatins A, B and C (141–143); 2-hydroxycircumdatin C (202); jaspaquinol (203); largamides A, B and C (204–206); largamide D oxazolidine (207); Laurencia similis brominated metabolites (208,209); molassamide (210); myrothenone A (211); 42-hydroxy-palytoxin (212); plectosphaeroic acids A, B and C (213–215); puupehenone (216); Sinularia numerosa oxylipin (217); sipholenone E (218); spartinoxide (219); 23-nor-spiculoic acid B (220); tanikolide dimer (221); tamulamides A and B (222,223); terretonins E and F (224,225); and tetrangulol methyl ether (226).

5. Reviews on Marine Pharmacology

Several reviews covering both general and specific areas of marine preclinical pharmacology were published during 2009–2011: (a) marine pharmacology and marine pharmaceuticals: a renaissance in marine pharmacology: from preclinical curiosity to clinical reality; biologically active marine natural products; drug development from marine natural products; biotechnological potential of marine natural products; pharmaceuticals from marine natural products: surge or ebb?; marine pharmacology in Australia: the Roche Research Institute; the global marine pharmaceutical pipeline in 2010: U.S. Food and Drug Administration-approved compounds and those in Phase I, II and III of clinical development; marine drugs from sponge-microbe associations; cyanobacteria as an emerging source for drug discovery; marine invertebrates as a future therapeutic treasure; biodiversity conservation and marine natural products drug discovery; marine invertebrates as a source of guanidines with chemical and pharmacological significance; innovations in the field of marine natural products and a new wave of drugs; (b) antimicrobial marine pharmacology: antibacterial marine natural products; marine microbes and pharmaceutical development; marine microbe-derived antibacterial agents; antimicrobial peptides from marine invertebrates; novel anti-infective compounds from marine bacteria; conventional and unconventional antimicrobials from fish, marine invertebrates and microalgae; (c) antiviral marine pharmacology: antiviral lead compounds from marine sponges; potential anti-HIV agents from marine resources; marine compounds and their antiviral activities; marine organisms as a therapeutic source against herpes simplex virus infection; (d) antiparasitic,antituberculosis, antimalarial and antifungal marine pharmacology: antiparasitic marine invertebrate-derived small molecules; marine antileishmanial natural products; antituberculosis leads from marine microbial metabolites; antimalarial drug discovery from marine sources between January 2003 and December 2008; antimalarial marine natural products from 2006 to 2008; antimalarial marine compounds; (e) immuno- and anti-inflammatory marine pharmacology: marine natural product leads for treatment of inflammation; marine natural products targeting phospholipase A2; marine diterpene glycosides as anti-inflammatory agents; anti-inflammatory compounds from marine algae; (f) cardiovascular marine pharmacology: marine-derived angiotensin-I-converting enzyme inhibitors; (g) nervous system marine pharmacology: conotoxins as natural products drug leads; marine indole alkaloids as new drug leads for depression and anxiety; marine natural products and ion channel pharmacology; neuroprotective effects of marine algae; conopeptides as novel options for pain management; structure-activity studies with α-conotoxins as selective antagonists of nicotinic acetylcholine receptors; (h) miscellaneous molecular targets: calyculins and related marine natural products as serine threonine protein phosphatase inhibitors; NF-κB inhibition by marine natural products; protein kinase inhibitors from marine sponges.

6. Conclusions

The global marine preclinical and clinical pharmaceutical pipelines remain remarkably active one year after U.S. Food and Drug Administration approval of brentuximab vedotin (Adcetris®), a conjugate between a monoclonal antibody that targets the cell-membrane protein CD30, an antigen which is highly expressed in lymphoid tumors, and several units of the potent antimitotic agent monomethyl auristatin E, a synthetic analog of the marine compound dolastatin 10.

This review aims to continue contributing to the marine preclinical pipeline review series that was initiated in 1998 and reveals the breadth of preclinical pharmacological research during 2009–2011, resulting from the global research effort of chemists and pharmacologists from Australia, Belgium, Brazil, Canada, China, Colombia, Cuba, Egypt, Fiji, France, Germany, Indonesia, Israel, Italy, Japan, Luxemburg, Malaysia, Mexico, the Netherlands, New Caledonia, New Zealand, Norway, Panama, Papua New Guinea, Philippines, South Africa, South Korea, Singapore, Spain, Switzerland, Taiwan, Thailand, United Kingdom, Venezuela, Vietnam, and the United States. Thus, we feel confident to predict that the marine preclinical pharmaceutical pipeline will most probably continue to provide novel pharmacological lead compounds that will enrich the marine clinical pharmaceutical pipeline, which currently consists of 6 U.S. Food and Drug Administration-approved pharmaceuticals and 11 compounds in Phase I, II and III of clinical development and which may be viewed at.

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    Hohmann C., Schneider K., Bruntner C., Irran E., Nicholson G., Bull A.T., Jones A.L., Brown R., Stach J.E., Goodfellow M., et al. Caboxamycin, a new antibiotic of the benzoxazole family produced by the deep-sea strain Streptomyces sp. NTK 937. J. Antibiot. 2009;62:99-104.

    Not in our library10.1038/ja.2008.24

  38. 38.

    Choi H., Engene N., Smith J.E., Preskitt L.B., Gerwick W.H. Crossbyanols A–D, toxic brominated polyphenyl ethers from the hawai’ian bloom-forming cyanobacterium Leptolyngbya crossbyana. J. Nat. Prod. 2010;73:517-522.

    Not in our library10.1021/np900661g

  39. 39.

    Bontemps N., Bry D., Lopez-Legentil S., Simon-Levert A., Long C., Banaigs B. Structures and antimicrobial activities of pyridoacridine alkaloids isolated from different chromotypes of the ascidian Cystodytes dellechiajei. J. Nat. Prod. 2010;73:1044-1048.

    Not in our library10.1021/np900751k

  40. 40.

    Wright A.D., McCluskey A., Robertson M.J., MacGregor K.A., Gordon C.P., Guenther J. Anti-malarial, anti-algal, anti-tubercular, anti-bacterial, anti-photosynthetic, and anti-fouling activity of diterpene isonitriles from the tropical marine sponge Cymbastela hooperi. Org. Biomol. Chem. 2011;9:400-407.

    Not in our library10.1039/c0ob00326c

  41. 41.

    Tadesse M., Tabudravu J.N., Jaspars M., Strom M.B., Hansen E., Andersen J.H., Kristiansen P.E., Haug T. The antibacterial ent-eusynstyelamide B and eusynstyelamides D, E, and F from the arctic bryozoan Tegella cf. spitzbergensis. J. Nat. Prod. 2011;74:837-841.

    Not in our library10.1021/np100499c

  42. 42.

    Tello E., Castellanos L., Arevalo-Ferro C., Duque C. Cembranoid diterpenes from the caribbean sea whip Eunicea knighti. J. Nat. Prod. 2009;72:1595-1602.

    Not in our library10.1021/np9002492

  43. 43.

    Isnansetyo A., Kamei Y. Anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of MC21-B, an antibacterial compound produced by the marine bacterium Pseudoalteromonas phenolica O-BC30T. Int. J. Antimicrob. Agents. 2009;34:131-135.

    Not in our library10.1016/j.ijantimicag.2009.02.009

  44. 44.

    Keffer J.L., Plaza A., Bewley C.A. Motualevic acids A–F, antimicrobial Acids from the Sponge Siliquariaspongia sp. Org. Lett. 2009;11:1087-1090.

    Not in our library10.1021/ol802890b

  45. 45.

    Engelhardt K., Degnes K.F., Kemmler M., Bredholt H., Fjaervik E., Klinkenberg G., Sletta H., Ellingsen T.E., Zotchev S.B. Production of a new thiopeptide antibiotic, TP-1161, by a marine Nocardiopsis Species. Appl. Environ. Microbiol. 2010;76:4969-4976.

    Not in our library10.1128/aem.00741-10

  46. 46.

    Stout E.P., Hasemeyer A.P., Lane A.L., Davenport T.M., Engel S., Hay M.E., Fairchild C.R., Prudhomme J., Le R.K., Aalbersberg W., et al. Antibacterial neurymenolides from the fijian red alga Neurymenia fraxinifolia. Org. Lett. 2009;11:225-228.

    Not in our library10.1021/ol8024814

  47. 47.

    Feher D., Barlow R., McAtee J., Hemscheidt T.K. Highly brominated antimicrobial metabolites from a marine Pseudoalteromonas sp. J. Nat. Prod. 2010;73:1963-1966.

    Not in our library10.1021/np100506z

  48. 48.

    Correa H., Aristizabal F., Duque C., Kerr R. Cytotoxic and antimicrobial activity of pseudopterosins and seco-Pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of san andres and providencia islands (Southwest Caribbean Sea). Mar. Drugs. 2011;9:334-343.

    Not in our library10.3390/md9030334

  49. 49.

    Till M., Prinsep M.R. 5-Bromo-8-methoxy-1-methyl-β-carboline, an alkaloid from the New Zealand marine bryozoan Pterocella vesiculosa. J. Nat. Prod. 2009;72:796-798.

    Not in our library10.1021/np8007655

  50. 50.

    Matsuda S., Adachi K., Matsuo Y., Nukina M., Shizuri Y. Salinisporamycin, a novel metabolite from Salinispora arenicola. J. Antibiot. 2009;62:519-526.

    Not in our library10.1038/ja.2009.75

  51. 51.

    Tadesse M., Strom M.B., Svenson J., Jaspars M., Milne B.F., Torfoss V., Andersen J.H., Hansen E., Stensvag K., Haug T. Synoxazolidinones A and B: Novel bioactive alkaloids from the ascidian Synoicum pulmonaria. Org. Lett. 2010;12:4752-4755.

    Not in our library10.1021/ol101707u

  52. 52.

    DiGirolamo J.A., Li X.C., Jacob M.R., Clark A.M., Ferreira D. Reversal of fluconazole resistance by sulfated sterols from the marine sponge Topsentia sp. J. Nat. Prod. 2009;72:1524-1528.

    Not in our library10.1021/np900177m

  53. 53.

    Nishimura S., Arita Y., Honda M., Iwamoto K., Matsuyama A., Shirai A., Kawasaki H., Kakeya H., Kobayashi T., Matsunaga S., et al. Marine antifungal theonellamides target 3β-hydroxysterol to activate rho1 signaling. Nat. Chem. Biol. 2010;6:519-526.

    Not in our library10.1038/nchembio.387

  54. 54.

    Carroll A.R., Duffy S., Avery V.M. Citronamides A and B, tetrapeptides from the australian sponge Citronia astra. J. Nat. Prod. 2009;72:764-768.

    Not in our library10.1021/np800832w

  55. 55.

    Yuan W.H., Yi Y.H., Tang H.F., Liu B.S., Wang Z.L., Sun G.Q., Zhang W., Li L., Sun P. Antifungal triterpene glycosides from the sea cucumber Bohadschia marmorata. Planta Med. 2009;75:168-173.

    Not in our library10.1055/s-0028-1088348

  56. 56.

    El-Gendy M.M., El-Bondkly A.M. Production and genetic improvement of a novel antimycotic agent, saadamycin, against dermatophytes and other clinical fungi from endophytic Streptomyces sp. Hedaya 48. J. Ind. Microbiol. Biotechnol. 2010;37:831-841.

    Not in our library10.1007/s10295-010-0729-2

  57. 57.

    Plaza A., Bifulco G., Keffer J.L., Lloyd J.R., Baker H.L., Bewley C.A. Celebesides A-C and theopapuamides B-D, depsipeptides from an indonesian sponge that inhibit HIV-1 entry. J. Org. Chem. 2009;74:504-512.

    Not in our library10.1021/jo802232u

  58. 58.

    Taglialatela-Scafati O., Fattorusso E., Romano A., Scala F., Barone V., Cimino P., Stendardo E., Catalanotti B., Persico M., Fattorusso C. Insight into the mechanism of action of plakortins, Simple 1,2-Dioxane antimalarials. Org. Biomol. Chem. 2010;8:846-856.

    Not in our library10.1039/b918600j

  59. 59.

    Lebouvier N., Jullian V., Desvignes I., Maurel S., Parenty A., Dorin-Semblat D., Doerig C., Sauvain M., Laurent D. Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a vanuatu marine sponge Pseudoceratina sp. Mar. Drugs. 2009;7:640-653.

    Not in our library10.3390/md7040640

  60. 60.

    Laville R., Thomas O.P., Berrue F., Marquez D., Vacelet J., Amade P. Bioactive guanidine alkaloids from two caribbean marine sponges. J. Nat. Prod. 2009;72:1589-1594.

    Not in our library10.1021/np900244g

  61. 61.

    Lin A.S., Stout E.P., Prudhomme J., Le R.K., Fairchild C.R., Franzblau S.G., Aalbersberg W., Hay M.E., Kubanek J. Bioactive bromophycolides R–U from the Fijian red alga Callophycus serratus. J. Nat. Prod. 2010;73:275-278.

    Not in our library10.1021/np900686w

  62. 62.

    Davis R.A., Duffy S., Avery V.M., Camp D., Hooper J.N.A., Quinn R.J. (+)-7-bromotrypargine:An antimalarial β-Carboline from the australian marine sponge Ancorina sp. Tetrahedron Lett. 2010;51:583-585.

    Not in our library10.1016/j.tetlet.2009.11.055

  63. 63.

    Wright A.D., Lang-Unnasch N. Diterpene formamides from the tropical marine sponge Cymbastela hooperi and their antimalarial activity in vitro. J. Nat. Prod. 2009;72:492-495.

    Not in our library10.1021/np800654w

  64. 64.

    Jiménez-Romero C., Ortíz I., Vicente J., Vera B., Rodríguez A.D., Nam S., Jove R. Bioactive cycloperoxides isolated from the puerto rican sponge Plakortis halichondrioides. J. Nat. Prod. 2010;73:1694-1700.

    Not in our library10.1021/np100461t

  65. 65.

    Linington R.G., Clark B.R., Trimble E.E., Almanza A., Urena L.D., Kyle D.E., Gerwick W.H. Antimalarial peptides from marine cyanobacteria: Isolation and structural elucidation of gallinamide A. J. Nat. Prod. 2009;72:14-17.

    Not in our library10.1021/np8003529

  66. 66.

    Ueoka R., Nakao Y., Kawatsu S., Yaegashi J., Matsumoto Y., Matsunaga S., Furihata K., van Soest R.W., Fusetani N. Gracilioethers A–C, antimalarial metabolites from the marine sponge Agelas gracilis. J. Org. Chem. 2009;74:4203-4207.

    Not in our library10.1021/jo900380f

  67. 67.

    Wattanapiromsakul C., Plubrukarn A., Suwanborirux K. 8-Isocyanoamphilecta-11(20),15-diene, a new antimalarial isonitrile diterpene from the sponge Ciocalapata sp. Can. J. Chem. 2009;87:612-618.

    Not in our library10.1139/v09-030

  68. 68.

    Tripathi A., Puddick J., Prinsep M.R., Rottmann M., Tan L.T. Lagunamides A and B: Cytotoxic and antimalarial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod. 2010;73:1810-1814.

    Not in our library10.1021/np100442x

  69. 69.

    Fattorusso C., Persico M., Calcinai B., Cerrano C., Parapini S., Taramelli D., Novellino E., Romano A., Scala F., Fattorusso E., et al. Manadoperoxides A–D from the indonesian sponge Plakortis cfr. simplex. Further insights on the structure-activity relationships of simple 1,2-dioxane antimalarials. J. Nat. Prod. 2010;73:1138-1145.

    Not in our library10.1021/np100196b

  70. 70.

    Yamada M., Takahashi Y., Kubota T., Fromont J., Ishiyama A., Otoguro K., Yamada H., Omura S., Kobayashi J. Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-Epoxymanzamine A, and 3,4-Dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp. Tetrahedron. 2009;65:2313-2317.

    Not in our library10.1016/j.tet.2009.01.032

  71. 71.

    Wei X., Nieves K., Rodríguez A.D. Neopetrosiamine A, biologically active bis-piperidine alkaloid from the caribbean sea sponge Neopetrosia proxima. Bioorg. Med. Chem. Lett. 2010;20:5905-5908.

    Not in our library10.1016/j.bmcl.2010.07.084

  72. 72.

    Yang X., Davis R.A., Buchanan M.S., Duffy S., Avery V.M., Camp D., Quinn R.J. Antimalarial bromotyrosine derivatives from the australian marine sponge Hyattella sp. J. Nat. Prod. 2010;73:985-987.

    Not in our library10.1021/np900834g

  73. 73.

    Dos Santos A.O., Britta E.A., Bianco E.M., Ueda-Nakamura T., Filho B.P., Pereira R.C., Nakamura C.V. 4-Acetoxydolastane diterpene from the brazilian brown alga Canistrocarpus cervicornis as antileishmanial agent. Mar. Drugs. 2011;9:2369-2383.

    Not in our library10.3390/md9112369

  74. 74.

    Vik A., Proszenyak A., Vermeersch M., Cos P., Maes L., Gundersen L.L. Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; Identification of hits for visceral leishmaniasis and chagas disease. Molecules. 2009;14:279-288.

    Not in our library10.3390/molecules14010279

  75. 75.

    Sanchez L.M., Lopez D., Vesely B.A., Della T.G., Gerwick W.H., Kyle D.E., Linington R.G. Almiramides A–C: Discovery and development of a new class of leishmaniasis lead compounds. J. Med. Chem. 2010;53:4187-4197.

    Not in our library10.1021/jm100265s

  76. 76.

    Davis R.A., Sykes M., Avery V.M., Camp D., Quinn R.J. Convolutamines I and J, antitrypanosomal alkaloids from the bryozoan Amathia tortusa. Bioorg. Med. Chem. 2011;19:6615-6619.

    Not in our library10.1016/j.bmc.2011.06.006

  77. 77.

    Scala F., Fattorusso E., Menna M., Taglialatela-Scafati O., Tierney M., Kaiser M., Tasdemir D. Bromopyrrole alkaloids as lead compounds against protozoan parasites. Mar. Drugs. 2010;8:2162-2174.

    Not in our library10.3390/md8072162

  78. 78.

    Cantillo-Ciau Z., Moo-Puc R., Quijano L., Freile-Pelegrin Y. The tropical brown alga Lobophora variegata: A source of antiprotozoal compounds. Mar. Drugs. 2010;8:1292-1304.

    Not in our library10.3390/md8041292

  79. 79.

    Rubio B.K., Tenney K., Ang K.H., Abdulla M., Arkin M., McKerrow J.H., Crews P. The marine sponge Diacarnus bismarckensis as a source of peroxiterpene inhibitors of Trypanosoma brucei, the causative agent of sleeping sickness. J. Nat. Prod. 2009;72:218-222.

    Not in our library10.1021/np800711a

  80. 80.

    Ma W.S., Mutka T., Vesley B., Amsler M.O., McClintock J.B., Amsler C.D., Perman J.A., Singh M.P., Maiese W.M., Zaworotko M.J., et al. Norselic acids A–E, highly oxidized anti-infective steroids that deter mesograzer predation, from the antarctic sponge Crella sp. J. Nat. Prod. 2009;72:1842-1846.

    Not in our library10.1021/np900382x

  81. 81.

    Regalado E.L., Tasdemir D., Kaiser M., Cachet N., Amade P., Thomas O.P. Antiprotozoal steroidal saponins from the marine sponge Pandaros acanthifolium. J. Nat. Prod. 2010;73:1404-1410.

    Not in our library10.1021/np100348x

  82. 82.

    Feng Y., Davis R.A., Sykes M., Avery V.M., Camp D., Quinn R.J. Antitrypanosomal cyclic polyketide peroxides from the australian marine sponge Plakortis sp. J. Nat. Prod. 2010;73:716-719.

    Not in our library10.1021/np900535z

  83. 83.

    Pimentel-Elardo S.M., Kozytska S., Bugni T.S., Ireland C.M., Moll H., Hentschel U. Anti-parasitic compounds from Streptomyces sp. strains isolated from mediterranean sponges. Mar. Drugs. 2010;8:373-380.

    Not in our library10.3390/md8020373

  84. 84.

    Vicente J., Vera B., Rodríguez A.D., Rodríguez-Escudero I., Raptis R.G. Euryjanicin A: A new cycloheptapeptide from the caribbean marine sponge Prosuberites laughlini. Tetrahedron Lett. 2009;50:4571-4574.

    Not in our library10.1016/j.tetlet.2009.05.067

  85. 85.

    Pruksakorn P., Arai M., Kotoku N., Vilcheze C., Baughn A.D., Moodley P., Jacobs W.R., Kobayashi M. Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria. Bioorg. Med. Chem. Lett. 2010;20:3658-3663.

    Not in our library10.1016/j.bmcl.2010.04.100

  86. 86.

    Cheng S.Y., Chuang C.T., Wang S.K., Wen Z.H., Chiou S.F., Hsu C.H., Dai C.F., Duh C.Y. Antiviral and anti-inflammatory diterpenoids from the soft coral Sinularia gyrosa. J. Nat. Prod. 2010;73:1184-1187.

    Not in our library10.1021/np100185a

  87. 87.

    Cheng S.Y., Wang S.K., Chiou S.F., Hsu C.H., Dai C.F., Chiang M.Y., Duh C.Y. Cembranoids from the octocoral Sarcophyton ehrenbergi. J. Nat. Prod. 2010;73:197-203.

    Not in our library10.1021/np900693r

  88. 88.

    Palem J.R., Bedadala G.R., El Sayed K.A., Hsia S.C. Manzamine a as a novel inhibitor of herpes simplex virus type-1 replication in cultured corneal cells. Planta Med. 2011;77:46-51.

    Not in our library10.1055/s-0030-1250093

  89. 89.

    Ding L., Munch J., Goerls H., Maier A., Fiebig H.H., Lin W.H., Hertweck C. Xiamycin, a pentacyclic indolosesquiterpene with selective anti-HIV activity from a bacterial mangrove endophyte. Bioorg. Med. Chem. Lett. 2010;20:6685-6687.

    Not in our library10.1016/j.bmcl.2010.09.010

  90. 90.

    Fan G., Li Z., Shen S., Zeng Y., Yang Y., Xu M., Bruhn T., Bruhn H., Morschhauser J., Bringmann G., et al. Baculiferins A–O, O-Sulfated pyrrole alkaloids with anti-HIV-1 activity, from the chinese marine sponge Iotrochota baculifera. Bioorg. Med. Chem. 2010;18:5466-5474.

    Not in our library10.1016/j.bmc.2010.06.052

  91. 91.

    Li Y., Carbone M., Vitale R.M., Amodeo P., Castelluccio F., Sicilia G., Mollo E., Nappo M., Cimino G., Guo Y.W., et al. Rare casbane diterpenoids from the Hainan soft coral Sinularia depressa. J. Nat. Prod. 2010;73:133-138.

    Not in our library10.1021/np900484k

  92. 92.

    Chakraborty K., Lipton A.P., Paulraj R., Chakraborty R.D. Guaiane sesquiterpenes from seaweed Ulva fasciata delile and their antibacterial properties. Eur. J. Med. Chem. 2010;45:2237-2244.

    Not in our library10.1016/j.ejmech.2010.01.065

  93. 93.

    Kemami Wangun H.V., Wood A., Fiorilla C., Reed J.K., McCarthy P.J., Wright A.E. Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii. J. Nat. Prod. 2010;73:712-715.

    Not in our library10.1021/np900526y

  94. 94.

    Mondol M.A., Kim J.H., Lee M.A., Tareq F.S., Lee H.S., Lee Y.J., Shin H.J. Ieodomycins A–D, antimicrobial fatty acids from a marine Bacillus sp. J. Nat. Prod. 2011;74:1606-1612.

    Not in our library10.1021/np200223r

  95. 95.

    Yao G., Kondratyuk T.P., Tan G.T., Pezzuto J.M., Chang L.C. Bioactive sulfated sesterterpene alkaloids and sesterterpene sulfates from the marine sponge Fasciospongia sp. J. Nat. Prod. 2009;72:319-323.

    Not in our library10.1021/np8005343

  96. 96.

    Elsebai M.F., Kehraus S., Lindequist U., Sasse F., Shaaban S., Gutschow M., Josten M., Sahl H.G., König G.M. Antimicrobial phenalenone derivatives from the marine-derived fungus Coniothyrium cereale. Org. Biomol. Chem. 2011;9:802-808.

    Not in our library10.1039/c0ob00625d

  97. 97.

    Devi P., Wahidullah S., Rodrigues C., Souza L.D. The sponge-associated bacterium Bacillus licheniformis SAB1: A source of antimicrobial compounds. Mar. Drugs. 2010;8:1203-1212.

    Not in our library10.3390/md8041203

  98. 98.

    Kamei Y., Sueyoshi M., Hayashi K., Terada R., Nozaki H. The novel anti-Propionibacterium acnes compound, sargafuran, found in the marine brown alga Sargassum macrocarpum. J. Antibiot. 2009;62:259-263.

    Not in our library10.1038/ja.2009.25

  99. 99.

    Smyrniotopoulos V., Vagias C., Rahman M.M., Gibbons S., Roussis V. Structure and antibacterial activity of brominated diterpenes from the red alga Sphaerococcus coronopifolius. Chem. Biodivers. 2010;7:186-195.

    Not in our library10.1002/cbdv.200800309

  100. 100.

    Mukai H., Kubota T., Aoyama K., Mikami Y., Fromont J., Kobayashi J. Tyrokeradines A and B, new bromotyrosine alkaloids with an imidazolyl-quinolinone moiety from a verongid sponge. Bioorg. Med. Chem. Lett. 2009;19:1337-1339.

    Not in our library10.1016/j.bmcl.2009.01.056

  101. 101.

    Li C., Haug T., Moe M.K., Styrvold O.B., Stensvag K. Centrocins: Isolation and characterization of novel dimeric antimicrobial peptides from the green sea urchin, Strongylocentrotus droebachiensis. Dev. Comp. Immunol. 2010;34:959-968.

    Not in our library10.1016/j.dci.2010.04.004

  102. 102.

    Galinier R., Roger E., Sautiere P.E., Aumelas A., Banaigs B., Mitta G. Halocyntin and papillosin, two new antimicrobial peptides isolated from hemocytes of the solitary tunicate, Halocynthia papillosa. J. Pept. Sci. 2009;15:48-55.

    Not in our library10.1002/psc.1101

  103. 103.

    Sperstad S.V., Haug T., Vasskog T., Stensvag K. Hyastatin, a glycine-rich multi-domain antimicrobial peptide isolated from the spider crab (Hyas araneus) hemocytes. Mol. Immunol. 2009;46:2604-2612.

    Not in our library10.1016/j.molimm.2009.05.002

  104. 104.

    Heo S.J., Hwang J.Y., Choi J.I., Han J.S., Kim H.J., Jeon Y.J. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown alga, a potent α-glucosidase and α-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur. J. Pharmacol. 2009;615:252-256.

    Not in our library10.1016/j.ejphar.2009.05.017

  105. 105.

    Li Y., Zhang Y., Shen X., Guo Y.W. A novel sesquiterpene quinone from hainan sponge Dysidea villosa. Bioorg. Med. Chem. Lett. 2009;19:390-392.

    Not in our library10.1016/j.bmcl.2008.11.068

  106. 106.

    Zhang Y., Li Y., Guo Y.W., Jiang H.L., Shen X. A sesquiterpene quinone, dysidine, from the sponge Dysidea villosa, activates the insulin pathway through inhibition of PTP ases. Acta Pharmacol. Sin. 2009;30:333-345.

    Not in our library10.1038/aps.2009.5

  107. 107.

    Asolkar R.N., Freel K.C., Jensen P.R., Fenical W., Kondratyuk T.P., Park E.J., Pezzuto J.M. Arenamides A–C, cytotoxic NFκB inhibitors from the marine actinomycete Salinispora arenicola. J. Nat. Prod. 2009;72:396-402.

    Not in our library10.1021/np800617a

  108. 108.

    Youssef D.T., Ibrahim A.K., Khalifa S.I., Mesbah M.K., Mayer A.M., van Soest R.W. New anti-inflammatory sterols from the red sea sponges Scalarispongia aqabaensis and Callyspongia siphonella. Nat. Prod. Commun. 2010;5:27-31.

    Not in our library

  109. 109.

    Jean Y.H., Chen W.F., Sung C.S., Duh C.Y., Huang S.Y., Lin C.S., Tai M.H., Tzeng S.F., Wen Z.H. Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats. Br. J. Pharmacol. 2009;158:713-725.

    Not in our library10.1111/j.1476-5381.2009.00323.x

  110. 110.

    Shi Y.P., Wei X., Rodríguez I.I., Rodríguez A.D., Mayer A.M.S. New terpenoid constituents of the Southwestern Caribbean sea whip Pseudopterogorgia elisabethae (Bayer) including a unique pentanorditerpene. Eur. J. Org. Chem. 2009;4:493-502.

    Not in our library

  111. 111.

    Li Y.X., Li Y., Lee S.H., Qian Z.J., Kim S.K. Inhibitors of oxidation and matrix metalloproteinases, floridoside, and d-isofloridoside from marine red alga Laurencia undulata. J. Agric. Food Chem. 2010;58:578-586.

    Not in our library10.1021/jf902811j

  112. 112.

    Malloy K.L., Villa F.A., Engene N., Matainaho T., Gerwick L., Gerwick W.H. Malyngamide 2, an oxidized lipopeptide with nitric oxide inhibiting activity from a papua new guinea marine cyanobacterium. J. Nat. Prod. 2011;74:95-98.

    Not in our library10.1021/np1005407

  113. 113.

    Villa F.A., Lieske K., Gerwick L. Selective MyD88-dependent pathway inhibition by the cyanobacterial natural product malyngamide F acetate. Eur. J. Pharmacol. 2010;629:140-146.

    Not in our library10.1016/j.ejphar.2009.12.002

  114. 114.

    Kim A.R., Shin T.S., Lee M.S., Park J.Y., Park K.E., Yoon N.Y., Kim J.S., Choi J.S., Jang B.C., Byun D.S., et al. Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties. J. Agric. Food Chem. 2009;57:3483-3489.

    Not in our library10.1021/jf900820x

  115. 115.

    Belmiro C.L., Castelo-Branco M.T., Melim L.M., Schanaider A., Elia C., Madi K., Pavao M.S., de Souza H.S. Unfractionated heparin and new heparin analogues from ascidians (chordate-tunicate) ameliorate colitis in rats. J. Biol. Chem. 2009;284:11267-11278.

    Not in our library10.1074/jbc.m807211200

  116. 116.

    Hanif N., Ohno O., Kitamura M., Yamada K., Uemura D. Symbiopolyol, a VCAM-1 inhibitor from a symbiotic dinoflagellate of the jellyfish Mastigias papua. J. Nat. Prod. 2010;73:1318-1322.

    Not in our library10.1021/np100221k

  117. 117.

    Costantino V., Fattorusso E., Mangoni A., Perinu C., Cirino G., de Gruttola G.L., Roviezzo F. Tedanol: A potent anti-inflammatory ent-pimarane diterpene from the caribbean sponge Tedania ignis. Bioorg. Med. Chem. 2009;17:7542-7547.

    Not in our library10.1016/j.bmc.2009.09.010

  118. 118.

    Liu C.Y., Hwang T.L., Lin M.R., Chen Y.H., Chang Y.C., Fang L.S., Wang W.H., Wu Y.C., Sung P.J. Carijoside A, a bioactive sterol glycoside from an octocoral Carijoa sp. (Clavulariidae). Mar. Drugs. 2010;8:2014-2020.

    Not in our library10.3390/md8072014

  119. 119.

    Cheng S.Y., Huang Y.C., Wen Z.H., Chiou S.F., Wang S.K., Hsu C.H., Dai C.F., Duh C.Y. Novel sesquiterpenes and norergosterol from the soft corals Nephthea erecta and Nephthea chabroli. Tetrahedron Lett. 2009;50:802-806.

    Not in our library

  120. 120.

    De Marino S., Festa C., D’Auria M.V., Bourguet-Kondracki M.L., Petek S., Debitus C., Andres R.M., Terencio M.C., Paya M., Zampella A. Coscinolactams A and B: New nitrogen-containing sesterterpenoid from the marine sponge Coscinoderma mathewsi exerting anti-inflammatory Properties. Tetrahedron. 2009;65:2905-2909.

    Not in our library10.1016/j.tet.2009.02.016

  121. 121.

    Cheng S.Y., Wen Z.H., Wang S.K., Chiou S.F., Hsu C.H., Dai C.F., Chiang M.Y., Duh C.Y. Unprecedented hemiketal cembranolides with anti-inflammatory activity from the soft coral Lobophytum durum. J. Nat. Prod. 2009;72:152-155.

    Not in our library10.1021/np800686k

  122. 122.

    Cheng S.Y., Wen Z.H., Wang S.K., Chiou S.F., Hsu C.H., Dai C.F., Duh C.Y. Anti-inflammatory cembranolides from the soft coral Lobophytum durum. Bioorg. Med. Chem. 2009;17:3763-3769.

    Not in our library10.1016/j.bmc.2009.04.053

  123. 123.

    Cheng S.Y., Chuang C.T., Wen Z.H., Wang S.K., Chiou S.F., Hsu C.H., Dai C.F., Duh C.Y. Bioactive norditerpenoids from the soft coral Sinularia gyrosa. Bioorg. Med. Chem. 2010;18:3379-3386.

    Not in our library10.1016/j.bmc.2010.04.012

  124. 124.

    Chen B.W., Chao C.H., Su J.H., Wen Z.H., Sung P.J., Sheu J.H. Anti-inflammatory eunicellin-based diterpenoids from the cultured soft coral Klyxum simplex. Org. Biomol. Chem. 2010;8:2363-2366.

    Not in our library10.1039/b926353e

  125. 125.

    Wanzola M., Furuta T., Kohno Y., Fukumitsu S., Yasukochi S., Watari K., Tanaka C., Higuchi R., Miyamoto T. Four new cembrane diterpenes isolated from an okinawan soft coral Lobophytum crassum with inhibitory effects on nitric oxide production. Chem. Pharm. Bull. 2010;58:1203-1209.

    Not in our library10.1248/cpb.58.1203

  126. 126.

    Festa C., de Marino S., Sepe V., Monti M.C., Luciano P., D’Auria M.V. Perthamides C and D, two new potent anti-inflammatory cyclopeptides from a solomon lithistid sponge Theonella swinhoei. Tetrahedron. 2009;65:10424-10429.

    Not in our library10.1016/j.tet.2009.10.026

  127. 127.

    Appleton D.R., Chuen C.S., Berridge M.V., Webb V.L., Copp B.R. Rossinones A and B, biologically active meroterpenoids from the antarctic ascidian, Aplidium species. J. Org. Chem. 2009;74:9195-9198.

    Not in our library10.1021/jo901846j

  128. 128.

    Cheng S.Y., Huang Y.C., Wen Z.H., Hsu C.H., Wang S.K., Dai C.F., Duh C.Y. New 19-oxygenated and 4-methylated steroids from the formosan soft coral Nephthea chabroli. Steroids. 2009;74:543-547.

    Not in our library10.1016/j.steroids.2009.02.004

  129. 129.

    Cheng S.Y., Wen Z.H., Chiou S.F., Tsai C.W., Wang S.K., Hsu C.H., Dai C.F., Chiang M.Y., Wang W.H., Duh C.Y. Ceramide and cerebrosides from the octocoral Sarcophyton ehrenbergi. J. Nat. Prod. 2009;72:465-468.

    Not in our library10.1021/np800362g

  130. 130.

    Lin W.Y., Su J.H., Lu Y., Wen Z.H., Dai C.F., Kuo Y.H., Sheu J.H. Cytotoxic and anti-inflammatory cembranoids from the dongsha atoll soft coral Sarcophyton crassocaule. Bioorg. Med. Chem. 2010;18:1936-1941.

    Not in our library10.1016/j.bmc.2010.01.036

  131. 131.

    Wu S.L., Su J.H., Wen Z.H., Hsu C.H., Chen B.W., Dai C.F., Kuo Y.H., Sheu J.H. Simplexins A–I, eunicellin-based diterpenoids from the soft coral Klyxum simplex. J. Nat. Prod. 2009;72:994-1000.

    Not in our library10.1021/np900064a

  132. 132.

    Costantino V., Fattorusso E., Mangoni A., Teta R., Panza E., Ianaro A. Terpioside B, a difucosyl GSL from the marine sponge Terpios sp. is a potent inhibitor of NO release. Bioorg. Med. Chem. 2010;18:5310-5315.

    Not in our library10.1016/j.bmc.2010.05.048

  133. 133.

    Kwan J.C., Eksioglu E.A., Liu C., Paul V.J., Luesch H. Grassystatins A–C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J. Med. Chem. 2009;52:5732-5747.

    Not in our library10.1021/jm9009394

  134. 134.

    Takei M., Umeyama A., Shoji N., Hashimoto T. Polyacetylenediols regulate the function of human monocyte-derived dendritic cells. Int. Immunopharmacol. 2010;10:913-921.

    Not in our library10.1016/j.intimp.2010.05.002

  135. 135.

    Shim S.Y., Choi J.S., Byun D.S. Inhibitory effects of phloroglucinol derivatives isolated from Ecklonia stolonifera on FcεRI expression. Bioorg. Med. Chem. 2009;17:4734-4739.

    Not in our library10.1016/j.bmc.2009.04.050

  136. 136.

    Strangman W.K., Kwon H.C., Broide D., Jensen P.R., Fenical W. Potent inhibitors of pro-inflammatory cytokine production produced by a marine-derived bacterium. J. Med. Chem. 2009;52:2317-2327.

    Not in our library10.1021/jm801110j

  137. 137.

    Dai Z., Zhang H., Zhang Y., Wang H. Chemical properties and immunostimulatory activity of a water-soluble polysaccharide from the clam of Hyriopsis cumingii lea. Carbohydr. Polym. 2009;77:365-369.

    Not in our library10.1016/j.carbpol.2009.01.003

  138. 138.

    Orsi C.F., Colombari B., Callegari F., Todaro A.M., Ardizzoni A., Rossini G.P., Blasi E., Peppoloni S. Yessotoxin inhibits phagocytic activity of macrophages. Toxicon. 2010;55:265-273.

    Not in our library10.1016/j.toxicon.2009.07.033

  139. 139.

    Inutsuka A., Goda M., Fujiyoshi Y. Calyculin A-induced neurite retraction is critically dependent on actomyosin activation but not on polymerization state of microtubules. Biochem. Biophys. Res. Commun. 2009;390:1160-1166.

    Not in our library10.1016/j.bbrc.2009.10.108

  140. 140.

    Sakurada T., Gill M.B., Frausto S., Copits B., Noguchi K., Shimamoto K., Swanson G.T., Sakai R. Novel N-methylated 8-oxoisoguanines from pacific sponges with diverse neuroactivities. J. Med. Chem. 2010;53:6089-6099.

    Not in our library10.1021/jm100490m

  141. 141.

    Choi H., Pereira A.R., Cao Z., Shuman C.F., Engene N., Byrum T., Matainaho T., Murray T.F., Mangoni A., Gerwick W.H. The hoiamides, structurally intriguing neurotoxic lipopeptides from papua new guinea marine cyanobacteria. J. Nat. Prod. 2010;73:1411-1421.

    Not in our library10.1021/np100468n

  142. 142.

    Pereira A.R., Cao Z., Engene N., Soria-Mercado I.E., Murray T.F., Gerwick W.H. Palmyrolide A, an unusually stabilized neuroactive macrolide from palmyra atoll cyanobacteria. Org. Lett. 2010;12:4490-4493.

    Not in our library10.1021/ol101752n

  143. 143.

    Zhao J., Li L., Ling C., Li J., Pang J.Y., Lin Y.C., Liu J., Huang R., Wang G.L., Pei Z., et al. Marine compound xyloketal B protects PC12 cells against OGD-induced cell damage. Brain Res. 2009;1302:240-247.

    Not in our library10.1016/j.brainres.2009.09.034

  144. 144.

    Soria-Mercado I.E., Pereira A., Cao Z., Murray T.F., Gerwick W.H. Alotamide A, a novel neuropharmacological agent from the marine cyanobacterium Lyngbya bouillonii. Org. Lett. 2009;11:4704-4707.

    Not in our library10.1021/ol901438b

  145. 145.

    Davis R.A., Fechner G.A., Sykes M., Garavelas A., Pass D.M., Carroll A.R., Addepalli R., Avery V.M., Hooper J.N., Quinn R.J. (−)-Dibromophakellin: An α2B adrenoceptor agonist isolated from the australian marine sponge, Acanthella costata. Bioorg. Med. Chem. 2009;17:2497-2500.

    Not in our library10.1016/j.bmc.2009.01.065

  146. 146.

    Suna H., Arai M., Tsubotani Y., Hayashi A., Setiawan A., Kobayashi M. Dysideamine, a new sesquiterpene aminoquinone, protects hippocampal neuronal cells against iodoacetic acid-induced cell death. Bioorg. Med. Chem. 2009;17:3968-3972.

    Not in our library10.1016/j.bmc.2009.04.025

  147. 147.

    Balansa W., Islam R., Fontaine F., Piggott A.M., Zhang H., Webb T.I., Gilbert D.F., Lynch J.W., Capon R.J. Ircinialactams: Subunit-selective glycine receptor modulators from Australian sponges of the family irciniidae. Bioorg. Med. Chem. 2010;18:2912-2919.

    Not in our library10.1016/j.bmc.2010.03.002

  148. 148.

    Tapiolas D.M., Bowden B.F., Abou-Mansour E., Willis R.H., Doyle J.R., Muirhead A.N., Liptrot C., Llewellyn L.E., Wolff C.W., Wright A.D., et al. Eusynstyelamides A, B, and C, nNOS inhibitors, from the Ascidian Eusynstyela latericius. J. Nat. Prod. 2009;72:1115-1120.

    Not in our library10.1021/np900099j

  149. 149.

    Tseng Y.J., Wen Z.H., Dai C.F., Chiang M.Y., Sheu J.H. Nanolobatolide, a new C18 metabolite from the formosan soft coral Sinularia nanolobata. Org. Lett. 2009;11:5030-5032.

    Not in our library10.1021/ol901990c

  150. 150.

    Lin Z., Antemano R.R., Hughen R.W., Tianero M.D., Peraud O., Haygood M.G., Concepcion G.P., Olivera B.M., Light A., Schmidt E.W. Pulicatins A–E, neuroactive thiazoline metabolites from cone snail-associated bacteria. J. Nat. Prod. 2010;73:1922-1926.

    Not in our library10.1021/np100588c

  151. 151.

    Perry V.H., Nicoll J.A., Holmes C. Microglia in neurodegenerative disease. Nat. Rev. Neurol. 2010;6:193-201.

    Not in our library10.1038/nrneurol.2010.17

  152. 152.

    Teruya T., Sasaki H., Fukazawa H., Suenaga K. Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium Lyngbya sp.: Isolation, stereostructure, and biological activity. Org. Lett. 2009;11:5062-5065.

    Not in our library10.1021/ol9020546

  153. 153.

    Henrich C.J., Robey R.W., Takada K., Bokesch H.R., Bates S.E., Shukla S., Ambudkar S.V., McMahon J.B., Gustafson K.R. Botryllamides: Natural product inhibitors of ABCG2. ACS Chem. Biol. 2009;4:637-647.

    Not in our library10.1021/cb900134c

  154. 154.

    Li Y., Qian Z.J., Ryu B., Lee S.H., Kim M.M., Kim S.K. Chemical components and its antioxidant properties in vitro: An edible marine brown alga, Ecklonia cava. Bioorg. Med. Chem. 2009;17:1963-1973.

    Not in our library10.1016/j.bmc.2009.01.031

  155. 155.

    Parys S., Kehraus S., Krick A., Glombitza K.W., Carmeli S., Klimo K., Gerhauser C., Konig G.M. In vitro chemopreventive potential of fucophlorethols from the brown alga Fucus vesiculosus L. by anti-oxidant activity and inhibition of selected cytochrome P450 enzymes. Phytochemistry. 2010;71:221-229.

    Not in our library10.1016/j.phytochem.2009.10.020

  156. 156.

    Mita M., Yoshikuni M., Ohno K., Shibata Y., Paul-Prasanth B., Pitchayawasin S., Isobe M., Nagahama Y. A relaxin-like peptide purified from radial nerves induces oocyte maturation and ovulation in the starfish, Asterina pectinifera. Proc. Natl. Acad. Sci. USA. 2009;106:9507-9512.

    Not in our library10.1073/pnas.0900243106

  157. 157.

    Tsubosaka Y., Murata T., Kinoshita K., Yamada K., Uemura D., Hori M., Ozaki H. Halichlorine is a novel L-type Ca2+ channel inhibitor isolated from the marine sponge Halichondria okadai Kadota. Eur. J. Pharmacol. 2010;628:128-131.

    Not in our library10.1016/j.ejphar.2009.11.026

  158. 158.

    Pereira A., Cao Z., Murray T.F., Gerwick W.H. Hoiamide A, a sodium channel activator of unusual architecture from a consortium of two papua new guinea cyanobacteria. Chem. Biol. 2009;16:893-906.

    Not in our library10.1016/j.chembiol.2009.06.012

  159. 159.

    Ohkawa Y., Miki K., Suzuki T., Nishio K., Sugita T., Kinoshita K., Takahashi K., Koyama K. Antiangiogenic metabolites from a marine-derived fungus, Hypocrea vinosa. J. Nat. Prod. 2010;73:579-582.

    Not in our library10.1021/np900698p

  160. 160.

    Morgan J.B., Mahdi F., Liu Y., Coothankandaswamy V., Jekabsons M.B., Johnson T.A., Sashidhara K.V., Crews P., Nagle D.G., Zhou Y.D. The marine sponge metabolite mycothiazole: A novel prototype mitochondrial complex I inhibitor. Bioorg. Med. Chem. 2010;18:5988-5994.

    Not in our library10.1016/j.bmc.2010.06.072

  161. 161.

    Mao S.C., Liu Y., Morgan J.B., Jekabsons M.B., Zhou Y.D., Nagle D.G. Lipophilic 2,5-disubstituted pyrroles from the marine sponge Mycale sp. Inhibit mitochondrial respiration and HIF-1 Activation. J. Nat. Prod. 2009;72:1927-1936.

    Not in our library10.1021/np900444m

  162. 162.

    Nakamura K., Tachikawa Y., Ohno O., Kitamura M., Suganuma M., Uemura D. Neocomplanines A and B, a complanine family isolated from the marine fireworm. J. Nat. Prod. 2010;73:303-305.

    Not in our library10.1021/np900694j

  163. 163.

    Dang Y., Low W.K., Xu J., Gehring N.H., Dietz H.C., Romo D., Liu J.O. Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII. J. Biol. Chem. 2009;284:23613-23621.

    Not in our library10.1074/jbc.m109.009985

  164. 164.

    Iwamoto M., Shimizu H., Muramatsu I., Oiki S.A. Cytotoxic peptide from a marine sponge exhibits ion channel activity through vectorial-insertion into the membrane. FEBS Lett. 2010;584:3995-3999.

    Not in our library10.1016/j.febslet.2010.08.007

  165. 165.

    Field J.J., Singh A.J., Kanakkanthara A., Halafihi T., Northcote P.T., Miller J.H. Microtubule-stabilizing activity of zampanolide, a potent macrolide isolated from the tongan marine sponge Cacospongia mycofijiensis. J. Med. Chem. 2009;52:7328-7332.

    Not in our library10.1021/jm901249g

  166. 166.

    Forestier R., Merchant C.E., de Voogd N.J., Matainaho T., Kieffer T.J., Anderson R.J. Aloketals A and B, sesterterpenoids from the marine sponge Hamigera species that activate the cAMP cell signalings pathway. Org. Lett. 2009;11:5166-5169.

    Not in our library10.1021/ol902066e

  167. 167.

    Seo C., Sohn J.H., Oh H., Kim B.Y., Ahn J.S. Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060. Bioorg. Med. Chem. Lett. 2009;19:6095-6097.

    Not in our library10.1016/j.bmcl.2009.09.025

  168. 168.

    Williams D.E., Amlani A., Dewi A.S., Patrick B.O., van Ofwegen L., Mui A.L.F., Andersen R.J. Australin E isolated from the soft coral Cladiella sp. collected in pohnpei activates the inositol 5-phosphatase SHIP1. Aust. J. Chem. 2010;63:895-900.

    Not in our library10.1071/ch10053

  169. 169.

    Rubio B.K., Parrish S.M., Yoshida W., Schupp P.J., Schils T., Williams P.G. Depsipeptides from a guamanian marine cyanobacterium, Lyngbya bouillonii, with selective inhibition of serine proteases. Tetrahedron Lett. 2010;51:6718-6721.

    Not in our library10.1016/j.tetlet.2010.10.062

  170. 170.

    Sisay M.T., Hautmann S., Mehner C., Konig G.M., Bajorath J., Gutschow M. Inhibition of human leukocyte elastase by brunsvicamides A–C: Cyanobacterial cyclic peptides. Chem. Med. Chem. 2009;4:1425-1429.

    Not in our library10.1002/cmdc.200900139

  171. 171.

    McCulloch M.W., Bugni T.S., Concepcion G.P., Coombs G.S., Harper M.K., Kaur S., Mangalindan G.C., Mutizwa M.M., Veltri C.A., Virshup D.M., et al. Carteriosulfonic acids A–C, GSK-3β inhibitors from a Carteriospongia sp. J. Nat. Prod. 2009;72:1651-1656.

    Not in our library10.1021/np900336f

  172. 172.

    Williams D.E., Hollander I., Feldberg L., Frommer E., Mallon R., Tahir A., Van Soest S.R., Andersen R.J. Scalarane-based sesterterpenoid RCE-protease inhibitors isolated from the indonesian marine sponge Carteriospongia foliascens. J. Nat. Prod. 2009;72:1106-1109.

    Not in our library10.1021/np900042r

  173. 173.

    Buchanan M.S., Carroll A.R., Wessling D., Jobling M., Avery V.M., Davis R.A., Feng Y., Hooper J.N., Quinn R.J. Clavatadines C–E, guanidine alkaloids from the australian sponge Suberea clavata. J. Nat. Prod. 2009;72:973-975.

    Not in our library10.1021/np8008013

  174. 174.

    Whitson E.L., Bugni T.S., Chockalingam P.S., Concepcion G.P., Feng X., Jin G., Harper M.K., Mangalindan G.C., McDonald L.A., Ireland C.M. Fibrosterol sulfates from the philippine sponge Lissodendoryx (Acanthodoryx) fibrosa: Sterol dimers that inhibit PKCzeta. J. Org. Chem. 2009;74:5902-5908.

    Not in our library10.1021/jo900844r

  175. 175.

    Rateb M.E., Houssen W.E., Schumacher M., Harrison W.T., Diederich M., Ebel R., Jaspars M. Bioactive diterpene derivatives from the marine sponge Spongionella sp. J. Nat. Prod. 2009;72:1471-1476.

    Not in our library10.1021/np900233c

  176. 176.

    Cui C.M., Li X.M., Li C.Y., Sun H.F., Gan S.S., Wang B.G. Benzodiazepine alkaloids from marine-derived endophytic fungus Aspergillus ochraceus. Helv. Chim. Acta. 2009;92:1366-1370.

    Not in our library10.1002/hlca.200900084

  177. 177.

    Robinson S.J., Hoobler E.K., Riener M., Loveridge S.T., Tenney K., Valeriote F.A., Holman T.R., Crews P. Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. J. Nat. Prod. 2009;72:1857-1863.

    Not in our library10.1021/np900465e

  178. 178.

    Matthew S., Paul V.J., Luesch H. Largamides A–C, tiglic acid-containing cyclodepsipeptides with elastase-inhibitory activity from the marine cyanobacterium Lyngbya confervoides. Planta Med. 2009;75:528-533.

    Not in our library10.1055/s-0029-1185332

  179. 179.

    Matthew S., Ratnayake R., Becerro M.A., Ritson-Williams R., Paul V.J., Luesch H. Intramolecular modulation of serine protease inhibitor activity in a marine cyanobacterium with antifeedant properties. Mar. Drugs. 2010;8:1803-1816.

    Not in our library10.3390/md8061803

  180. 180.

    Qin J., Su H., Zhang Y., Gao J., Zhu L., Wu X., Pan H., Li X. Highly brominated metabolites from marine red alga Laurencia similis inhibit protein tyrosine phosphatase 1B. Bioorg. Med. Chem. Lett. 2010;20:7152-7154.

    Not in our library10.1016/j.bmcl.2010.08.144

  181. 181.

    Gunasekera S.P., Miller M.W., Kwan J.C., Luesch H., Paul V.J. Molassamide, a depsipeptide serine protease inhibitor from the marine cyanobacterium Dichothrix utahensis. J. Nat. Prod. 2010;73:459-462.

    Not in our library10.1021/np900603f

  182. 182.

    Feng Z., Leutou A.S., Yang G., Nenkep V.N., Siwe X.N., Choi H.D., Kang J.S., Son B.W. Bioactive cyclopentenone derivatives from marine isolates of fungi. Bull. Korean Chem. Soc. 2009;30:2345-2350.

    Not in our library10.5012/bkcs.2009.30.10.2345

  183. 183.

    Ciminiello P., Dell’Aversano C., Dello I.E., Fattorusso E., Forino M., Grauso L., Tartaglione L., Florio C., Lorenzon P., de Bortoli M., et al. Stereostructure and biological activity of 42-Hydroxy-palytoxin: A new palytoxin analogue from Hawaiian Palythoa subspecies. Chem. Res. Toxicol. 2009;22:1851-1859.

    Not in our library10.1021/tx900259v

  184. 184.

    Carr G., Tay W., Bottriell H., Andersen S.K., Mauk A.G., Andersen R.J. Plectosphaeroic Acids A, B, and C, indoleamine 2,3-Dioxygenase inhibitors produced in culture by a marine isolate of the fungus Plectosphaerella cucumerina. Org. Lett. 2009;11:2996-2999.

    Not in our library10.1021/ol900972j

  185. 185.

    Yamashita T., Nakao Y., Matsunaga S., Oikawa T., Imahara Y., Fusetani N. A new antiangiogenic C24 oxylipin from the soft coral Sinularia numerosa. Bioorg. Med. Chem. 2009;17:2181-2184.

    Not in our library10.1016/j.bmc.2008.10.083

  186. 186.

    Jain S., Abraham I., Carvalho P., Kuang Y.H., Shaala L.A., Youssef D.T., Avery M.A., Chen Z.S., El Sayed K.A. Sipholane triterpenoids: Chemistry, reversal of ABCB1/P-Glycoprotein-Mediated multidrug resistance, and pharmacophore modeling. J. Nat. Prod. 2009;72:1291-1298.

    Not in our library10.1021/np900091y

  187. 187.

    Elsebai M.F., Kehraus S., Gutschow M., Konig G.M. Spartinoxide, a new enantiomer of A82775C with inhibitory activity toward HLE from the marine-derived fungus Phaeosphaeria spartinae. Nat. Prod. Commun. 2010;5:1071-1076.

    Not in our library

  188. 188.

    Ankisetty S., Gochfeld D.J., Diaz M.C., Khan S.I., Slattery M. Chemical constituents of the deep reef caribbean sponges Plakortis angulospiculatus and Plakortis halichondrioides and their anti-inflammatory activities. J. Nat. Prod. 2010;73:1494-1498.

    Not in our library10.1021/np100233d

  189. 189.

    Gutierrez M., Andrianasolo E.H., Shin W.K., Goeger D.E., Yokochi A., Schemies J., Jung M., France D., Cornell-Kennon S., Lee E., et al. Structural and synthetic investigations of tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the madagascar marine cyanobacterium Lyngbya majuscula. J. Org. Chem. 2009;74:5267-5275.

    Not in our library10.1021/jo900578j

  190. 190.

    Truxal L.T., Bourdelais A.J., Jacocks H., Abraham W.M., Baden D.G. Characterization of tamulamides A and B, polyethers isolated from the marine dinoflagellate Karenia brevis. J. Nat. Prod. 2010;73:536-540.

    Not in our library10.1021/np900541w

  191. 191.

    Lopez-Gresa M.P., Cabedo N., Gonzalez-Mas M.C., Ciavatta M.L., Avila C., Primo J. Terretonins E and F, inhibitors of the mitochondrial respiratory chain from the marine-derived fungus Aspergillus insuetus. J. Nat. Prod. 2009;72:1348-1351.

    Not in our library10.1021/np900085n

  192. 192.

    Choi Y., Jermihov K., Nam S.J., Sturdy M., Maloney K., Qiu X., Chadwick L.R., Main M., Chen S.N., Mesecar A.D., Farnsworth N.R., Pauli G.F., Fenical W., Pezzuto J.M., van Breemen R.B. Screening natural products for inhibitors of quinone reductase-2 using ultrafiltration LC-MS. Anal. Chem. 2011;83:1048-1052.

    Not in our library10.1021/ac1028424

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    Kwan J.C., Taori K., Paul V., Luesch H. Lyngbyastatins 8–10, elastase inhibitors with cyclic depsipeptide scaffolds isolated from the marine cyanobacterium Lyngbya semiplena. Mar. Drugs. 2009;7:528-538.

    Not in our library10.3390/md7040528

  194. 194.

    Glaser K.B., Mayer A.M. A renaissance in marine pharmacology: From preclinical curiosity to clinical reality. Biochem. Pharmacol. 2009;78:440-448.

    Not in our library10.1016/j.bcp.2009.04.015

  195. 195.

    Nakamura K., Kitamura M., Uemura D. Biologically active marine natural products. Heterocycles. 2009;78:1-17.

    Not in our library10.3987/rev-08-637

  196. 196.

    Molinski T.F., Dalisay D.S., Lievens S.L., Saludes J.P. Drug development from marine natural products. Nat. Rev. Drug Discov. 2009;8:69-85.

    Not in our library10.1038/nrd2487

  197. 197.

    Fusetani N. Biotechnological potential of marine natural products. Pure Appl. Chem. 2010;82:17-26.

    Not in our library10.1351/pac-con-09-01-11

  198. 198.

    Hill R.T., Fenical W. Pharmaceuticals from marine natural products: Surge or Ebb? Curr. Opin. Biotechnol. 2010;21:777-779.

    Not in our library10.1016/j.copbio.2010.10.007

  199. 199.

    Rae I.D. Marine pharmacology in Australia. The roche research institute at dee why, new South Wales, 1974–81. Aust. J. Chem. 2010;63:855-861.

    Not in our library10.1071/ch10073

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    Mayer A.M., Glaser K.B., Cuevas C., Jacobs R.S., Kem W., Little R.D., McIntosh J.M., Newman D.J., Potts B.C., Shuster D.E. The odyssey of marine pharmaceuticals: A current pipeline perspective. Trends Pharmacol. Sci. 2010;31:255-265.

    Not in our library10.1016/j.tips.2010.02.005

  201. 201.
    Marine Drugs from Sponge-Microbe Association—A Review · 2010
    No notice
  202. 202.

    Singh R.K., Tiwari S.P., Rai A.K., Mohapatra T.M. Cyanobacteria: An emerging source for drug discovery. J. Antibiot. 2011;64:401-412.

    Not in our library10.1038/ja.2011.21

  203. 203.

    Park Y. Mining invertebrate natural products for future therapeutic treasure. Nat. Prod. Commun. 2011;6:1403-1408.

    Not in our library

  204. 204.

    Kingston D.G. Modern natural products drug discovery and its relevance to biodiversity conservation. J. Nat. Prod. 2011;74:496-511.

    Not in our library10.1021/np100550t

  205. 205.

    Ebada S.S., Proksch P. Chemical and pharmacological significance of natural guanidines from marine invertebrates. Mini-Rev. Med. Chem. 2011;11:225-246.

    Not in our library10.2174/138955711795049862

  206. 206.

    Montaser R., Luesch H. Marine natural products: A new wave of drugs? Future Med. Chem. 2011;3:1475-1489.

    Not in our library10.4155/fmc.11.118

  207. 207.

    Hughes C.C., Fenical W. Antibacterials from the Sea. Chem. Eur J. 2010;16:12512-12525.

    Not in our library10.1002/chem.201001279

  208. 208.

    Waters A.L., Hill R.T., Place A.R., Hamann M.T. The expanding role of marine microbes in pharmaceutical development. Curr. Opin. Biotechnol. 2010;21:780-786.

    Not in our library10.1016/j.copbio.2010.09.013

  209. 209.

    Lu X., Cao X., Liu X., Jiao B. Marine microbes-derived anti-bacterial agents. Mini-Rev. Med. Chem. 2010;10:1077-1090.

    Not in our library10.2174/1389557511009011077

  210. 210.

    Otero-Gonzalez A.J., Magalhaes B.S., Garcia-Villarino M., Lopez-Abarrategui C., Sousa D.A., Dias S.C., Franco O.L. Antimicrobial peptides from marine invertebrates as a new frontier for microbial infection control. FASEB J. 2010;24:1320-1334.

    Not in our library10.1096/fj.09-143388

  211. 211.

    Rahman H., Austin B., Mitchell W.J., Morris P.C., Jamieson D.J., Adams D.R., Spragg A.M., Schweizer M. Novel anti-infective compounds from marine bacteria. Mar. Drugs. 2010;8:498-518.

    Not in our library10.3390/md8030498

  212. 212.
    Conventional and Unconventional Antimicrobials from Fish, Marine Invertebrates and Micro-algae · 2010
    No notice
  213. 213.
    Antiviral Lead Compounds from Marine Sponges · 2010
    No notice
  214. 214.

    Vo T.S., Kim S.K. Potential anti-HIV agents from marine resources: An overview. Mar. Drugs. 2010;8:2871-2892.

    Not in our library10.3390/md8122871

  215. 215.

    Yasuhara-Bell J., Lu Y. Marine compounds and their antiviral activities. Antiviral Res. 2010;86:231-240.

    Not in our library10.1016/j.antiviral.2010.03.009

  216. 216.

    Vo T.S., Ngo D.H., Ta Q.V., Kim S.K. Marine organisms as a therapeutic source against herpes simplex virus infection. Eur. J. Pharm. Sci. 2011;44:11-20.

    Not in our library10.1016/j.ejps.2011.07.005

  217. 217.

    Watts K.R., Tenney K., Crews P. The structural diversity and promise of antiparasitic marine invertebrate-derived small molecules. Curr. Opin. Biotechnol. 2010;21:808-818.

    Not in our library10.1016/j.copbio.2010.09.015

  218. 218.

    Tempone A.G., de Oliveira M., Berlinck R.G. Current approaches to discover marine antileishmanial natural products. Planta Med. 2011;77:572-585.

    Not in our library10.1055/s-0030-1250663

  219. 219.

    Ashforth E.J., Fu C., Liu X., Dai H., Song F., Guo H., Zhang L. Bioprospecting for antituberculosis leads from microbial metabolites. Nat. Prod. Rep. 2010;27:1709-1719.

    Not in our library10.1039/c0np00008f

  220. 220.

    Peach K.C., Linington R.G. New innovations for an old infection: Antimalarial lead discovery from marine natural products during the period 2003–2008. Future Med. Chem. 2009;1:593-617.

    Not in our library10.4155/fmc.09.56

  221. 221.

    Gademann K., Kobylinska J. Antimalarial natural products of marine and freshwater origin. Chem. Rec. 2009;9:187-198.

    Not in our library10.1002/tcr.200900001

  222. 222.

    Fattorusso E., Taglialatela-Scafati O. Marine antimalarials. Mar. Drugs. 2009;7:130-152.

    Not in our library10.3390/md7020130

  223. 223.

    Villa F.A., Gerwick L. Marine natural product drug discovery: Leads for treatment of inflammation, cancer, infections, and neurological disorders. Immunopharmacol. Immunotoxicol. 2010;32:228-237.

    Not in our library10.3109/08923970903296136

  224. 224.

    Folmer F., Jaspars M., Schumacher M., Dicato M., Diederich M. Marine natural products targeting phospholipases A2. Biochem. Pharmacol. 2010;80:1793-1800.

    Not in our library10.1016/j.bcp.2010.08.024

  225. 225.

    Berrue F., McCulloch M.W., Kerr R.G. Marine diterpene glycosides. Bioorg. Med. Chem. 2011;19:6702-6719.

    Not in our library10.1016/j.bmc.2011.06.083

  226. 226.

    Jaswir I., Monsur H.A. Anti-inflammatory compounds of macro algae origin: A review. J. Med. Plants Res. 2011;5:7146-7154.

    Not in our library

  227. 227.
    Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry · 2010
    No notice
  228. 228.

    Halai R., Craik D.J. Conotoxins: Natural product drug leads. Nat. Prod. Rep. 2009;26:526-536.

    Not in our library10.1039/b819311h

  229. 229.

    Kochanowska-Karamyan A.J., Hamann M.T. Marine indole alkaloids: Potential new drug leads for the control of depression and anxiety. Chem. Rev. 2010;110:4489-4497.

    Not in our library10.1021/cr900211p

  230. 230.

    Teichert R.W., Olivera B.M. Natural products and ion channel pharmacology. Future Med. Chem. 2010;2:731-744.

    Not in our library10.4155/fmc.10.31

  231. 231.
    Neuroprotective Effects of Marine Algae · 2011
    No notice
  232. 232.

    Daly N.L., Craik D.J. Conopeptides as novel options for pain management. Drugs Future. 2011;36:25-32.

    Not in our library

  233. 233.

    Muttenthaler M., Akondi K.B., Alewood P.F. Structure-activity studies on alpha-conotoxins. Curr. Pharm. Des. 2011;17:4226-4241.

    Not in our library10.2174/138161211798999384

  234. 234.

    Fagerholm A.E., Habrant D., Koskinen A.M. Calyculins and related marine natural products as serine-threonine protein phosphatase PP1 and PP2A inhibitors and total syntheses of calyculin A, B, and C. Mar. Drugs. 2010;8:122-172.

    Not in our library10.3390/md80100122

  235. 235.

    Folmer F., Jaspars M., Solano G., Cristofanon S., Henry E., Tabudravu J., Black K., Green D.H., Küpper F.C., Aalbersberg W., et al. The inhibition of TNF-α-induced NF-κB activation by marine natural products. Biochem. Pharmacol. 2009;78:592-606.

    Not in our library10.1016/j.bcp.2009.05.009

  236. 236.

    Skropeta D., Pastro N., Zivanovic A. Kinase inhibitors from marine sponges. Mar. Drugs. 2011;9:2131-2154.

    Not in our library10.3390/md9102131

  237. 237.

    Senter P.D., Sievers E.L. The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat. Biotechnol. 2012;30:631-637.

    Not in our library10.1038/nbt.2289

  238. 238.

    The Global Marine Pharmaceutical Pipeline.

    Not in our library

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