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

Abstract

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 μm with SI > 1, respectively, indicating that these compounds were cytotoxic at concentrations values of 1.58, 1.98 and 2.04 μm, respectively.