Design, Synthesis, In Vitro Evaluation of Antitumor Activity, and Molecular Docking Studies of D-ring-opened Indazole-Matrine Derivatives as Potential Anticancer Agents

Hanqing Zhang; Siying Lu; Jamal A H Kowah; Suzhen Yan; Haixia Yu; Lisheng Wang

doi:10.1002/cbdv.202500358

Design, Synthesis, In Vitro Evaluation of Antitumor Activity, and Molecular Docking Studies of D-ring-opened Indazole-Matrine Derivatives as Potential Anticancer Agents

Chem Biodivers. 2025 Jun 27:e00358. doi: 10.1002/cbdv.202500358. Online ahead of print.

Authors

Hanqing Zhang¹, Siying Lu¹, Jamal A H Kowah², Suzhen Yan¹, Haixia Yu³, Lisheng Wang¹

Affiliations

¹ School of Medicine, Guangxi University, Nanning, China.
² School of Chemistry and Chemical Engineering, Guangxi University, Nanning, China.
³ School of Chemical Engineering, Jilin Vocational College of Industry and Technology, Jilin, China.

PMID: 40577423
DOI: 10.1002/cbdv.202500358

Abstract

To develop matrine derivatives with improved anticancer activity, we designed and synthesized 16 derivatives using matrine as the lead compound through drug splicing principles. Using the MTT assay, we evaluated their antiproliferative effects against three human cancer cell lines: cervical cancer (HeLa), hepatocellular carcinoma (Huh-7), and triple-negative breast cancer (MDA-MB-231). Most compounds demonstrated superior activity to matrine, with W12 showing the strongest effects (IC₅₀ values: 4.8 ± 0.33 µM for Huh-7, 8.03 ± 1.28 µM for MDA-MB-231, and 10.11 ± 0.39 µM for HeLa). W12 induced concentration-dependent morphological changes, G1 phase cell cycle arrest, apoptosis, and inhibited colony formation and migration. Molecular docking revealed that W12 forms hydrogen bonds and other interactions with TRK-related protein 5KVT. These findings suggest that W12 is a promising anticancer drug precursor.

Keywords: anticancer; derivatives; drug splicing; matrine.

Abstract

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