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

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 H-1 NMR, C-13 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 mu M), Bewo (0.68 mu M) and MCF-7 (3.74 mu M) cell lines than the positive agent cisplatin (9.97 mu M for A549, 10.46 mu M for Bewo, and 15.03 mu M for MCF-7), respectively.