Cytotoxic Activity of Some Pyrazolo[4,3-e][1,2,4]Triazines Against Human Cancer Cell Lines[1]

Abstract

The aim of this study is to investigate the potential cytotoxic effect of some synthesized pyrazolo[4,3-e] [1,2,4]triazine derivatives against four different tumor cell lines: PC-3 (prostate cancer), MCF-7 (breast cancer), H460 (non-small cell lung cancer cells), and Colo205 (colorectal adenocarcinoma). Cytotoxic effect was measured using MTT reduction assay. Several compounds demonstrated significant broad cytotoxic activity in low micromolar range. The screened pyrazolo[4,3-e][1,2,4]triazines were obtained in direct condensation of 5-acyl-1,2,4-triazines with hydrazine or its derivatives under acidic conditions in good yield. The mode of cyclocondensation is considerably dependent on the electronic nature of a phenyl ring substituent of the aromatic hydrazones: electron-donating substituents favor the cyclization in shorter time contrary to electronwithdrowing substituents which work favorable for the formation of pyrazolo[4,3-e][1,2,4]triazines in longer time. Nucleophilic substitution of methylsulfonyl group in the position 5 takes place with O-, N- and C-nucleophiles to yield related substitution products in high yields. 5-Hydrazino derivative 6 (Nu = NH-NH2, R2 = CH3, R3 = Ph) is useful for the preparation of 7, 8 and 9. Alkylation of the N-1 unsubstituted 4 (R1 = SCH3, R2 = CH3, R3 = H) provided mixture of 10 and 11.