Synthesis, biological evaluation and molecular docking of N, N’-bis([1,2,4]triazole[4,3-b][1,2,4,5]tetrazine-6-yl)alkylamine derivatives as potent c-Met antagonists

Abstract

A series of N, N’-bis([1,2,4]triazole[4,3- b][1,2,4,5]tetrazine-6-yl)alkylamine derivatives is designed, synthesized and evaluated for their inhibition activities against three tumor cell lines and c-Met kinase activity in vitro. These compounds are fully characterized by 1H NMR, 13C NMR, MS, IR and elemental analysis. Antitumor experiments indicate that some of these compounds exhibit significant inhibition activities against A549, Bewo and MCF-7 cancer cell lines. Among them, the IC50 values of 4a indicate better antitumor activities against the A549 (1.21 μM), Bewo (0.68 μM) and MCF-7 (3.74 μM) cell lines than the positive agent cisplatin (9.97 μM for A549, 10.46 μM for Bewo, and 15.03 μM for MCF-7), respectively.