Journal of The Serbian Chemical Society | 2019
Structure–activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives
Abstract
This paper presents the synthesis of some unique bi-heterocyclic hyb\xadrid molecules with a thiazole and an oxadiazole ring. The synthesis was ini\xadtiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate ( 1 ) to the corres\xadpond\xading 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide ( 2 ) by the reaction with hydra\xadzine hydrate in methanol. The treatment of the acid hydrazide, 2 , with carbon disulfide gave the bi-heterocyclic nucleophile, 5-[(2-amino-1,3- -thiazol-4-yl)\xadmethyl]-1,3,4-oxadiazole-2-thiol ( 3 ). Finally, the target com\xadpounds, 5a – o , were synthesized by stirring the nucleophile 3 with different electrophiles, 4a – o , in DMF using LiH as a base and an activator. The struc\xadtures of the newly syn\xadthesized molecules were confirmed through spectro\xadscopic techniques, such as IR, EI-MS, 1H-NMR and 13C-NMR. The structure– –activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholines\xadter\xadase, urease and a -glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.