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Letters in Drug Design & Discovery

Author(s): Bin Zhou, Lisheng Wang*, Yongquan Wei, Meiyan Jiang and Xingdong Wang

DOI: 10.2174/0115701808300981240408063655

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

Page: [3590 - 3603] Pages: 14

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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.

Graphical Abstract

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