Liu Ting-Ting, Xie Meng-Fan, Liu Xin, Li Rong-Tao, Bai Yao, Zhang Zhi-Jun
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Biomolecules. 2025 Mar 18;15(3):436. doi: 10.3390/biom15030436.
Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute hepatitis, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Despite several antiviral drugs, including interferon- and nucleotide derivatives, being approved for clinical treatment of HBV, critical issues remain unresolved, e.g., their low-to-moderate efficacy and adverse side effects, as well as resistant strains. In this study, twenty-three matrine derivatives were synthesized, and their antiviral effects against HBV were evaluated. Of these, eleven compounds inhibited HBeAg secretion significantly more than the positive control, lamivudine (3TC). Among the compounds synthesized in this study, compounds and had the most potent inhibitory activity, with IC value of 41.78 and 33.68 μM, respectively. Compounds , and were also subjected to molecular docking studies. These compounds inhibited viral gene expression and viral propagation in a cell culture model. Thus, we believe our compounds could serve as resource for antiviral drug development.
乙型肝炎病毒（HBV）是一种致病因子，常引发进行性肝脏疾病，导致急性肝炎、慢性肝炎、肝硬化，最终发展为肝细胞癌。尽管包括干扰素和核苷酸衍生物在内的几种抗病毒药物已被批准用于HBV的临床治疗，但关键问题仍未解决，例如它们的疗效低至中等、有副作用，以及存在耐药菌株。在本研究中，合成了23种苦参碱衍生物，并评估了它们对HBV的抗病毒作用。其中，11种化合物对HBeAg分泌的抑制作用明显强于阳性对照拉米夫定（3TC）。在本研究合成的化合物中，化合物 和 具有最强的抑制活性，IC值分别为41.78和33.68 μM。化合物 、 和 也进行了分子对接研究。这些化合物在细胞培养模型中抑制病毒基因表达和病毒繁殖。因此，我们认为我们的化合物可作为抗病毒药物开发的资源。
