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

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. K_i 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

Acknowledgements

The enzyme inhibition part of this study was carried out in Igdır University Research Laboratory Practice and Research Center (ALUM). The numerical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

Disclosure statement

All the authors have no conflict for the publication of this article.