Back close

Pharmacophore-Based 3D-QSAR Analysis of Thienyl Chalcones as a New Class of Human MAO-B Inhibitors: Investigation of Combined Quantum Chemical and Molecular Dynamics Approach.

Publication Type : Journal Article

Publisher : J Phys Chem B

Source : J Phys Chem B, Volume 121, Issue 6, p.1186-1203 (2017)

Url : https://pubmed.ncbi.nlm.nih.gov/28084742/

Keywords : Chalcones, Humans, Molecular Dynamics Simulation, Monoamine oxidase, Monoamine Oxidase Inhibitors, Quantitative Structure-Activity Relationship, Quantum theory

Campus : Kochi

School : School of Pharmacy

Center : Amrita Institute of Medical Science

Department : Pharmaceutical Chemistry & Analysis

Year : 2017

Abstract : Selective monoamine oxidase-B (MAO-B) inhibitors are imperative in the treatment of various neurodegenerative disorders. Herein, we describe the pharmacophore generation and atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses of previously reported thiophene-based hMAO-B inhibitors by our research group. The aim of this study was to identify the principal structural features that could potentially be responsible for the inhibitory activity of hMAO-B inhibitors. The best pharmacophore model generated was the four-point assay of AHRR.8. The pharmacophore model exhibited good correlation with its predictability of the statistically valid 3D-QSAR analyses. Density functional theory calculations were further employed on the lead molecule (2E)-1-(5-bromothiophen-2-yl)-3-[4-(dimethylamino) phenyl] prop-2-en-1-one (Tb5) to investigate the electrostatic potential surface and analyze the natural bond orbital toward the binding characteristics. Molecular dynamics simulations were performed to characterize the molecular level interactions and relative energies of the hMAO isoforms: hMAO-A and hMAO-B with three potent and selective hMAO-B inhibitors (Tb5, Tb6, and Tb9). The results of both continuous and accelerated molecular dynamics simulations demonstrate a distinct preference of the three ligands to bind to hMAO-B rather than hMAO-A.

Cite this Research Publication : Bijo Mathew, Adeniyi, A. A., Dev, S., Joy, M., Ucar, G., Mathew, G. Elizabeth, Singh-Pillay, A., and Soliman, M. E. S., “Pharmacophore-Based 3D-QSAR Analysis of Thienyl Chalcones as a New Class of Human MAO-B Inhibitors: Investigation of Combined Quantum Chemical and Molecular Dynamics Approach.”, J Phys Chem B, vol. 121, no. 6, pp. 1186-1203, 2017.

Admissions Apply Now