Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents
2020
Zhuocai Wei | Jie Tan | Xinhua Cui | Min Zhou | Yunhou Huang | Ning Zang | Zhaoni Chen | Wanxing Wei
Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ±: 12.78 &mu:M, SI (2b-3) = 11.03: IC50 (2b-1) = 96.64 ±: 28.99 &mu:M, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 &mu:M, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.
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