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

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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.

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Authors and Affiliations

  1. Faculty of Health, Muş Alparslan University, 49250, Muş, Turkey

    A. Cetin

  2. Health Services Vocational School, Igdir University, 76000, Igdir, Turkey

    F. Türkan

  3. Faculty of Health, Muş Alparslan University, 49250, Muş, Turkey

    E. Bursal

  4. Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, 560054, Bangalore, India

    M. Murahari

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Correspondence to E. Bursal.

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Cetin, A., Türkan, F., Bursal, E. et al. Synthesis, Characterization, Enzyme Inhibitory Activity, and Molecular Docking Analysis of a New Series of Thiophene-Based Heterocyclic Compounds. Russ J Org Chem 57, 598–604 (2021). https://doi.org/10.1134/S107042802104014X

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