Synthesis, anti-HIV and cytotoxicity evaluation of chiral 2,5-disubstituted 1,3,4-thiadiazole derivatives bearing the sulfonamide scaffold

In the present study, chiral 2-(4-substiuted phenyl)amino-5-[1-(4-substituted benzenesulphonamido)alkyl]-1,3,4-thiazdiazoles 5a-x were synthesized from enantiopure l-amino acids in a multistep sequence. The starting acids were reacted with arylsulphonyl chlorides to produce N-arylsulfonyl amino acids 1a-h, followed by esterification to obtain the corresponding esters 2a-h. Treatment of esters with hydrazine hydrate afforded the corresponding hydrazides 3a-h. The coupling of hydrazides with aryl isothiocyanates followed by cyclization gave the target thiadiazoles 5a-x in good yields. The new synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells using MTT assay. Compounds 5s, 5v and 5w showed IC50 values of > 1.58, >1.98 and > 2.04 mu m with SI > 1, respectively, indicating that these compounds were cytotoxic at concentrations values of 1.58, 1.98 and 2.04 mu m, respectively.