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

Muhammad Athar Abbasi, Muhammad Shahid Ramzan, Aziz Ur Rehman, Sabhat Zahra Siddiqui, Mubashir Hassan, Hussain Raza, Syed Adnan Ali Shah, Bushra Mirza, Sung-Yum Seo

Abstract


The present study represented the synthesis of some unique bi-he­terocyclic molecules hybrid 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 corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydrazine hydrate in methanol. The treatment of acid hydrazide, 2, with car­bon disulfide gave a 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 like 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 a-glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by the killing data of brine shrimps at various concentrations.


Keywords


1,3-Thiazole; 1,3,4-oxadiazole; acetylcholinesterase; butyrylcholinesterase; urease; glucosidase; molecular docking; brine shrimps

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DOI: https://doi.org/10.2298/10.2298/JSC180203019A

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