衣壳
苯并咪唑
体内
化学
效力
乙型肝炎病毒
IC50型
EC50型
病毒学
体外
铅化合物
药品
药理学
病毒
生物化学
生物
有机化学
生物技术
作者
Kun Du,Xianyang Wang,Yuxin Bai,Xue Zhao,Jia Xue,Li S,Youhua Xie,Zhipei Sang,Ting Yu,Xiaoquan Wang
标识
DOI:10.1016/j.ejmech.2024.116402
摘要
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.
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