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

Zhuocai Wei; Jie Tan; Xinhua Cui; Min Zhou; Yunhou Huang; Ning Zang; Zhaoni Chen; Wanxing Wei

doi:10.3390/molecules25153359

Molecules (Jul 2020)

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

Zhuocai Wei,
Jie Tan,
Xinhua Cui,
Min Zhou,
Yunhou Huang,
Ning Zang,
Zhaoni Chen,
Wanxing Wei

Affiliations

Zhuocai Wei: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Jie Tan: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Xinhua Cui: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Min Zhou: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Yunhou Huang: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
Ning Zang: School of Basic Medical Science, Guangxi Medical University, Nanning 530021, China
Zhaoni Chen: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China
Wanxing Wei: College of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China

DOI: https://doi.org/10.3390/molecules25153359
Journal volume & issue: Vol. 25, no. 15
p. 3359

Abstract

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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 μM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 μM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 μM, 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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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