Synthesis, Characterization, Enzyme Inhibitory Activity, and Molecular Docking Analysis of a New Series of Thiophene-Based Heterocyclic Compounds

Abstract

Abstract: 1-Phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide derivatives were designed and evaluated for their in vitro enzyme inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST). In particular, N,1-diphenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide (10) was found to be the best AChE inhibitor (Ki = 19.88±3.06 µM), [1-phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-yl](piperidin-1-yl)methanone (8) showed the highest inhibitory activity against BChE (Ki = 13.72±1.12 µM), and (morpholin-4-yl)[1-phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-yl]methanone (7) was found to be the best inhibitor for GST (Ki = 16.44±1.58 µM). Molecular docking studies revealed significant interactions at the enzyme active sites, and compounds 7, 8, and 10 exhibited good binding affinities for GST (–9.7 kcal/mol), BChE (–9.4 kcal/mol), and AChE (–9.3 kcal/mol), respectively. The results of the present study have good potential to contribute further structural modifications and pharmacological studies related to enzyme inhibitors. © 2021, Pleiades Publishing, Ltd.