New chalcone derivative, ethyl 2-(4-(3-(benzo[ b]thiophen-2-yl)acryloyl)phenoxy)acetate: synthesis, characterization, DFT study, enzyme inhibition activities and docking study

J Biomol Struct Dyn. 2022;40(22):12260-12267. doi: 10.1080/07391102.2021.1969287. Epub 2021 Aug 26.

Abstract

Chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2yl)acryloyl)phenoxy)acetate (I), was synthesized. Compound I was characterized by proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR), fourier transform infrared (FTIR) and mass (LC-ESI-MS/MS) spectroscopic methods. Density Functional Theory (DFT) calculations for compound I were performed at B3LYP/6-311++G(d,p) level. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound I were obtained. The evaluations reveal that the calculation results support the experimental results. The inhibition effects of compound I on cholinesterases and GST enzyme were investigated. Ki and inhibition concentration (IC50) values were calculated separately. Ki values of compound I were found for GST 14.19 ± 2.15, for AChE 11.13 ± 1.22 and for BChE 8.74 ± 0.76 recpectively. The docking analysis of compound I supported the enzym inhibition activity exhibiting high inhibition constant and binding energy for three receptors. Compound I is strongly bound to AChE, huBChE and Glutathione S-transferase with binding energies -11.24, -8.56 and -10.39 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

Keywords: Chalcone; DFT; cholinesterases; glutathione S-transferase; inhibition; molecular docking study.

MeSH terms

  • Acetates
  • Chalcone* / pharmacology
  • Chalcones* / pharmacology
  • Quantum Theory
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman
  • Tandem Mass Spectrometry
  • Thiophenes / pharmacology

Substances

  • Chalcones
  • Chalcone
  • Thiophenes
  • Acetates