Design, synthesis and bioactivity investigation of tetrandrine derivatives as potential anti-cancer agents

• Published in: MedChemComm 2018-07, Vol.9 (7), p.1131-1141
• Main Authors: Song, Junrong, Lan, Junjie, Chen, Chao, Hu, Shengcao, Song, Jialei, Liu, Wulin, Zeng, Xueyi, Lou, Huayong, Ben-David, Yaacov, Pan, Weidong
• Format: Article
• Language: English
• Subjects: Anticancer properties; Apoptosis; Biological activity; Biotechnology; Cancer; Cell death; Cytotoxicity; Derivatives; Sulfonamides; Tetrandrine; Tumor cell lines
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c8md00125a

Twenty-four 14-sulfonamide-tetrandrine derivatives as potential anti-cancer agents were synthesized. The synthetic derivatives were investigated for their cytotoxic activity against human cancer cell lines MDA-MB-231, PC3, WM9, HEL and K562. Initially, the IC 50 values (50% inhibitory concentrations) of all of the compounds were determined. These derivatives exhibited potent, but distinct, inhibitory effects on the above-mentioned cell lines. Among them, compound 23 , which was modified with a 2-naphthalenesulfonyl group at the 14-amino position, showed impressive inhibition of all five cancer cell lines, and especially of MDA-MB-231 cells with an IC 50 value of 1.18 ± 0.14 μM. Further mechanism exploration showed that 23 induced potent apoptotic cell death on MDA-MB-231 cancer cells in a concentration-dependent manner. The results revealed that 23 might be a potential anti-cancer drug candidate. Twenty-four 14-sulfonamide-tetrandrine derivatives were synthesized. Compound 23 exhibited growth inhibition of MDA-MB-231 cells with an IC 50 value of 1.18 ± 0.14 μM.