Synthesis, Characterization, Enzyme Inhibitory Activity, and Molecular Docking Analysis of a New Series of Thiophene-Based Heterocyclic Compounds
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, vol.57, no.4, pp.598-604, 2021 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 57 Issue: 4
- Publication Date: 2021
- Doi Number: 10.1134/s107042802104014x
- Journal Name: RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core
- Page Numbers: pp.598-604
- Keywords: enzyme inhibition, heterocyclic compounds, molecular docking, thiophene, pyrazole, DERIVATIVES
- Van Yüzüncü Yıl University Affiliated: No
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 (K-i = 19.88 +/- 3.06 mu M), [1-phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-yl](piperidin-1-yl)methanone (8) showed the highest inhibitory activity against BChE (K-i = 13.72 +/- 1.12 mu M), 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 (K-i = 16.44 +/- 1.58 mu M). 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.