title: Synthesis, structure analysis, and antitumor evaluation of 3,6-dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives.
abstract: 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 (IC(50) =0.57 μM) 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 mgkg(-1) body weight. Moreover, its acute toxicity was evaluated, and the i.p. LD(50) value was 325 mgkg(-1) in mice.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China. rgw@zjut.edu.cn
authors.forename: Guo-Wu
authors.initials: GW
authors.lastname: Rao
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Guo
authors.forename: Wei-Xiao
authors.initials: WX
authors.lastname: Hu
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring