A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer: Synthesis and its cytotoxic activity

A novel [1,2,41 triazolo pyrimidine-based phenyl-linked steroid dimer was designed, synthesized and evaluated for its cytotoxic activity against five human cancer cell lines and the cytotoxicity against human normal liver cell L-02. Compound 3 showed excellent cytotoxic activity and good selectivity between cancer and normal cells. Further mechanistic studies revealed that treatment of EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and time-dependent manner and induced apoptosis probably through the mitochondria] pathway accompanied with the decrease of mitochondrial membrane potential, activations of caspase-9/-3, cleavage of MDM2 as well as upregulation of the expressions of p53 and Bax. (C) 2013 Elsevier Masson SAS. All rights reserved.