Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (<i>E</i>)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

A series of oxime Cyclohexyl (<i>E</i>)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC₅₀ = 63.85 &#177; 6.26 &#956;M, SI = 13.41) and HBeAg (IC₅₀ = 49.39 &#177; 4.17 &#956;M, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC₅₀ = 234.2 &#177; 17.17 &#956;M, SI = 2.2) and HBeAg (IC₅₀ = 249.9 &#177; 21.51 &#956;M, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18&#8722;27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.

Abstract licence: CC BY

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