Regioselective synthesis and evaluation of novel sulfonamide 1,2,3-triazole derivatives as antitumor agents

A novel series of 1,2,3-triazole containing sulfonamide moiety was synthesized. Treatment of 4-acetyl 1,2,3-triazole 3 with different aldehydes gave alpha,beta-unsaturated ketones 4a-c. Condensation of 3 with dimethylformamide dimethylacetal (DMF-DMA) gave formimidamide 5. Chalcone 7 was achieved via two ways from the reaction of 5 with benzaldehyde or from treatment of 4a with DMF-DMA. Reaction of 7 with hydrazine hydrate afforded pyrazoline 8. 5-Methyl pyrazole 12 was synthesized from Claisen condensation reaction of 3 or 5 with ethyl acetate to give 1,3-diketone adduct 9 or 10, respectively, followed by treatment with hydrazine hydrate. 5-Aminopyrazole 17 was synthesized from the reaction of ester 13 or formimidamide ester 13a with acetonitrile to afford cyanoacetyl derivatives 14 or 15, respectively, followed by treatment with hydrazine hydrate. The new compounds were screened for their in vitro antitumor activity. The results of this investigation revealed that compounds 12, 7, and 17 had a significant anticancer activity against MCF-7 cancer cell line with IC50 values 12.4, 19.8, and 23.4 mu M, respectively, in relation to the standard drug, doxorubicin.