Design, Synthesis, and Biological Evaluation of Novel Trifluoromethylated Dipeptide Mimetics of Matijin-Su as Potent Anti-HBV Agents

Chem Biodivers. 2024 Dec 23:e202402061. doi: 10.1002/cbdv.202402061. Online ahead of print.

Abstract

A series of Matijin-Su (MTS) derivatives were designed, synthesized and their anti-hepatitis B virus (HBV) activities were evaluated in vitro. Twelve compounds displayed good inhibitory activity against HBV DNA replication with IC50 values at micromolar level (0.14-4.81 µM), and among them, compounds 13d, 13n, and 13o were selected for further study. Compound 13d suppressed the HBeAg secretion with IC50 value of 2.57 µM (SI = 4.31), while had no effect on HBsAg. However, compounds 13n and 13o showed no effect to both HBeAg and HBsAg. The molecular docking studies indicated that compound 13d could form H-bond interaction with protein residues of HBV core protein which deserves further study.

Keywords: anti‐hepatitis B virus (HBV) activity; dipeptide mimetics; molecular docking; synthesis; trifluoromethyl.