Investigation of cholinesterase and α-glucosidase enzyme activities, and molecular docking and dft studies for 1,2-disubstituted cyclopentane derivatives with phenyl and benzyl units

Artunç T., Çetinkaya Y., Taslimi P., Menzek A.

MOLECULAR DIVERSITY, cilt.29, sa.2, ss.1305-1321, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s11030-024-10911-y
  • Dergi Adı: MOLECULAR DIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, MEDLINE
  • Sayfa Sayıları: ss.1305-1321
  • Anahtar Kelimeler: AChE, BChE, Bromination, Density functional theory, α-Glucosidase
  • Atatürk Üniversitesi Adresli: Evet

Özet

Six known products (4-9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10-13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4-13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and alpha-glucosidase enzymes. All compounds 4-13 showed inhibition at nanomolar level with Ki values in the range of 45.53 +/- 7.35-631.96 +/- 18.88 nM for AChE, 84.30 +/- 9.92-622.10 +/- 35.14 nM for BChE, and 25.47 +/- 4.46-48.87 +/- 7.33 for alpha-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and alpha-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO-LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6-31 + G(d,p).