Design, Synthesis, and In vitro Biological Activities of Matrine Skeleton Derivatives as Potential Cancer Inhibitors

Bin      Zhou; Lisheng      Wang; Yongquan      Wei; Meiyan      Jiang; Xingdong      Wang

doi:10.2174/0115701808300981240408063655

Abstract

Background: Thirteen derivatives were designed and synthesized based on the excellent lead compound Matrine.

Objective: This study aimed to discover novel anticancer agents with superior anticancer activity and to support the discovery of new drugs.

Methods: The in vitro antiproliferative activity of all derivatives against four human cancer cells, A549, HGC-27, HCT-116, and HeLa, was determined by MTT. The best active compounds were subjected to cell cloning, migration, cell cycle and apoptosis, and molecular docking.

Results: Compound 5XI showed the best activity against all four cell lines, especially against A549 cells, with an IC₅₀ of 5.805 μmol/L. The antiproliferative activity of 5XI was much higher than that of matrine and only slightly weaker than that of Cisplatin, a multi-targeted small molecule inhibitor. 5XI also showed excellent inhibitory activity in cell cycle, apoptosis, cell scratch, and cell cloning assays and has shown good affinity in docking studies.

Conclusion: 5XI has excellent antiproliferative activity, significantly inhibits cell cloning and migration, affects cancer cell cycle distribution, and induces apoptosis in a concentration-dependent manner, making it a potential anticancer drug agent.

Keywords: Matrine, thiazole, imidazo[2, 1-b]thiazole, synthesis, antiproliferative, anticancer agents.

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DOI https://dx.doi.org/10.2174/0115701808300981240408063655	Print ISSN 1570-1808
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Letters in Drug Design & Discovery

Design, Synthesis, and In vitro Biological Activities of Matrine Skeleton Derivatives as Potential Cancer Inhibitors

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