2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans
Heegyu Kim, Ji-Yeon Hwang, Beomkoo Chung and 4 more
Marine Drugs · 2019
doi:10.3390/md17020133 (opens in a new tab)
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Abstract
Four 2-alkyl-4-hydroxyquinoline derivatives (<b>1</b>⁻<b>4</b>) were isolated from a semisolid rice culture of the marine-derived actinomycete <i>Streptomyces</i> sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds <b>1</b> and <b>2</b> exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound <b>1</b> acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus <i>Candida albicans</i>, with an IC<sub>50</sub> value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound <b>1</b> inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of <i>HWP1</i> and <i>ALS3</i> mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound <b>1</b>. These results indicate that compound <b>1</b> acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in <i>Candida albicans</i>.
Abstract licence: CC BY
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