{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T23:04:38Z","timestamp":1776035078881,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204243"],"award-info":[{"award-number":["82204243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["XDYC-QNRC-2023-0140"],"award-info":[{"award-number":["XDYC-QNRC-2023-0140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Talent Project of Yunnan Revitalization Talent Support Program","award":["82204243"],"award-info":[{"award-number":["82204243"]}]},{"name":"Young Talent Project of Yunnan Revitalization Talent Support Program","award":["XDYC-QNRC-2023-0140"],"award-info":[{"award-number":["XDYC-QNRC-2023-0140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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-\u03b1 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 4a and 4d had the most potent inhibitory activity, with IC50 value of 41.78 and 33.68 \u03bcM, respectively. Compounds 1h, 4a, and 4d 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.<\/jats:p>","DOI":"10.3390\/biom15030436","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T12:03:06Z","timestamp":1742299386000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design, Synthesis, and Bioevaluation of Matrine Derivatives as Potential Anti\u2013Hepatitis B Virus Agents"],"prefix":"10.3390","volume":"15","author":[{"given":"Ting-Ting","family":"Liu","sequence":"first","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Fan","family":"Xie","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Bai","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-8676","authenticated-orcid":false,"given":"Zhi-Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1021\/acs.jmedchem.3c00173","article-title":"Discovery of linvencorvir (RG7907), a hepatitis B virus core protein allosteric modulator, for the treatment of chronic HBV infection","volume":"66","author":"Zhang","year":"2023","journal-title":"J. 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