Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents.

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 them2b-3and2b-1showed 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.