Cytotoxic activity of some Pyrazolo[4,3-e][1,2,4]Triazines against human cancer cell lines

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.