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 hybrid molecules with a thiazole and an oxadiazole ring. The synthesis was initiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) to the corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydrazine 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)methyl]-1,3,4-oxadiazole-2-thiol (3). Finally, the target compounds, 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 structures of the newly synthesized molecules were confirmed through spectroscopic 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, butyrylcholinesterase, urease and -glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.

Keywords

• 1,3-thiazole
• 1,3,4-oxadiazole
• acetylcholinesterase
• butyrylcholine-esterase
• urease
• glucosidase
• molecular docking
• brine shrimps