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- Drug Discovery
- Pharmaceutical Science
- Molecular Medicine
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.