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

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 in vitro 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=0.57 mu M) was further evaluated in vivo against an A-549 xenograft in BALB/cA nude mice; it effected 76.4?% inhibition of tumor weight through intraperitoneal (i.p.) administration of 40 mg?kg-1 body weight. Moreover, its acute toxicity was evaluated, and the i.p. LD50 value was 325 mg?kg-1 in mice.