Synthesis, X-ray crystallographic analysis, and antitumor activity of 1-acyl-3,6-disubstituted phenyl-1,4-dihydro-1,2,4,5-tetrazines.
Eleven compounds of 1-acyl-3,6-disubstituted phenyl-1,4-dihydro-1,2,4,5-tetrazines were prepared from 3,6-disubstituted phenyl-1,2-dihydro-1,2,4,5-tetrazines and anhydrides or acyl chlorines, and their structures were confirmed by single-crystal X-ray diffraction and the semi-empirical calculation of PM3 method. This reaction yields the 1,4-dihydro derivatives rather than the 1,2-dihydro derivatives. The central six-membered ring of these compounds has an obvious boat conformation and therefore is not homoaromatic. Their antitumor activities were evaluated in vitro by the SRB method for A-549 cell and the MTT method for P-388 cells. The results show that there is one compound which is highly effective against A-549 cells and two compounds which are highly effective against P-388 cells. Thus, this compound possesses potential antitumor activities and is worth researching further.
Rao
Guo-Wu
GW
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
Hu
Wei-Xiao
WX
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds