Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents
- Bioorg Med Chem Lett. 2018 Feb 15;28(4):677-683. doi: 10.1016/j.bmcl.2018.01.017.
- 1. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
- 2. Suzhou Galaxy biopharma, CO., LTD., Suzhou, Jiangsu 215000, PR China.
- 3. Medical College of Guangxi University, Guangxi 530004, PR China.
- 4. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China. Electronic address: [email protected].
- 5. Medical College of Guangxi University, Guangxi 530004, PR China. Electronic address: [email protected].
Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as Anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against three human Cancer cell lines (SMMC-7721, A549 and CNE2). The results revealed that compound A6 and B21 displayed the most significant Anticancer activity against three Cancer cell lines with IC50 values in range of 3.42-8.05 μM, which showed better activity than the parent compound (Matrine) and positive control Cisplatin. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound A6 and B21 could significantly induce the Apoptosis of SMMC-7721 and CNE2 cells in a dose-dependent manner. The cell cycle analysis also revealed that compound A6 could cause cell cycle arrest of SMMC-7721 and CNE2 cells at G2/M phase.