Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors

Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better anti proliferative activity results with IC50 values from 0.13 mu M to 1.74 mu M than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DRS and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site. (C) 2019 Elsevier Masson SAS. All rights reserved.