Synthesis, Structure Analysis, and Antitumor Evaluation of 3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide Derivatives

Article abstract of DOI:10.1002/cmdc.201200109

3,6-Dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives were synthesized, and their structures were confirmed by single-crystal X-ray diffraction. This reaction yields the 1,4-dicarboxamide derivatives rather than the 1,2-dicarboxamide derivatives. Their invitro antitumor activities were evaluated against SGC-7901, HO-8910, MCF-7, and A-549 cells. The results showed several compounds to be endowed with cytotoxicity in the low micromolar range. One compound (IC₅₀=0.57μM) was further evaluated invivo against an A-549 xenograft in BALB/cA nude mice; it effected 76.4% inhibition of tumor weight through intraperitoneal (i.p.) administration of 40mgkg^-1 body weight. Moreover, its acute toxicity was evaluated, and the i.p. LD₅₀ value was 325mgkg^-1 in mice.