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

Cetin A., Turkan F., Bursal E., Murahari M.

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, cilt.57, sa.4, ss.598-604, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 57 Sayı: 4
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1134/s107042802104014x
  • Dergi Adı: RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core
  • Sayfa Sayıları: ss.598-604
  • Anahtar Kelimeler: enzyme inhibition, heterocyclic compounds, molecular docking, thiophene, pyrazole, DERIVATIVES
  • Van Yüzüncü Yıl Üniversitesi Adresli: Hayır

Özet

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.