Design, Synthesis, and in Vitro Biological Activities of Matrine Skeleton Derivatives As Potential Cancer Inhibitors

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.