2. Academic Validation
  3. Development of benzimidazole-based compounds as novel capsid assembly modulators for the treatment of HBV infection

Development of benzimidazole-based compounds as novel capsid assembly modulators for the treatment of HBV infection

  • Eur J Med Chem. 2024 May 5:271:116402. doi: 10.1016/j.ejmech.2024.116402.
Kaixin Du 1,  Xianyang Wang 2,  Yuxin Bai 2,  Xue Zhang 1,  Jie Xue 2,  Shanshan Li 2,  Youhua Xie 3,  Zhipei Sang 4,  Yu Tang 5,  Xin Wang 6
Affiliations

Affiliations

  • 1 Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
  • 2 Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
  • 3 Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infectious Diseases and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: yhxie@fudan.edu.cn.
  • 4 Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China. Electronic address: sangzhipei@126.com.
  • 5 Key Laboratory of Marine Drugs, Chinese Ministry of Education, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, 266237, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China. Electronic address: tangyu@ouc.edu.cn.
  • 6 Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China. Electronic address: xinwangPharm@hainanu.edu.cn.
PMID: 38636128 DOI: 10.1016/j.ejmech.2024.116402
Abstract

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV Infection. In this study, the hit compound CDI (IC50 = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their Antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC50 = 0.51 ± 0.20 μM, EC50 = 2.24 ± 0.43 μM, CC50 = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety.

Keywords

Benzimidazole derivatives; Capsid assembly modulators; HDI mouse model; Hepatitis B virus infection.

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