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

Xueling Meng; Xiaoshuang Shao; Anxiang Kuang; Bixue Xu; Xiaoping Zeng; Xiangkai Kong; Guangcan Xu; Gang Yu

doi:10.1002/cbdv.202402061

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.

Authors

Xueling Meng¹, Xiaoshuang Shao², Anxiang Kuang², Bixue Xu³, Xiaoping Zeng³, Xiangkai Kong⁴, Guangcan Xu⁵, Gang Yu⁶

Affiliations

¹ Guizhou Medical University, State key library of Functions and Applications of Medicinal Plants, Guizhou Science City, Baiyun District, Guiyang City, Guizhou Province, 550014, Guiyang, CHINA.
² Guizhou University of Traditional Chinese Medicine, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Science City, Baiyun District, Guiyang City, Guizhou Province, 550014, Guiyang, CHINA.
³ Guizhou Medical University, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Science City, Baiyun District, Guiyang City, Guizhou Province, 550014, Guiyang, CHINA.
⁴ Guizhou Medical University, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang City, Guizhou Province, 550004, Guiyang, CHINA.
⁵ Guizhou Medical University, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Science City，Baiyun District， Guiyang, 550014, Guiyang, CHINA.
⁶ Guizhou Medical University, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Science City，Baiyun District，Guiyang, 550014, Guiyang, CHINA.

PMID: 39714596
DOI: 10.1002/cbdv.202402061

Abstract

A series of Matijin-Su (MTS) derivatives were designed, synthesized and the anti-HBV activity evaluated in vitro. Twelve compounds displayed good inhibition on HBV DNA replication with micromolar IC50 values (0.14 - 4.81 μM), 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.

Keywords: Dipeptide Mimetics; Trifluoromethyl; anti-HBV Activity; molecular docking; synthesis.