Evaluation of O-methyl substituted quercetin analogues as DPP-4 Inhibitor: in silico study

Abstract

Quercetin having chromone nucleus is attracting high attention due to diverse pharmacological properties. Moreover, quercetin as a dipeptidyl peptidase IV (DPP-4) inhibitors are projected to have significant potential in the treatment of diabetes. In this study, in silico evaluation of O-methyl substituted quercetin analogues as DPP-4 Inhibitor have been reported. The 2D structures of quercetin and its O-CH₃ derivatives were prepared using the ACD chem sketch software and molecular docking was run by MVD 6.0 tool with the 3-dimensional (3D) crystal structure of Human dipeptidyl peptidase IV(DPP-4) (PDB ID: 4J3J, retrieved from RCSB-PDB. Molecular properties such as molecular weight of designed compounds, donated or accepted hydrogen count, rotatable bonds, aromatic rings, partition coefficient (log P), surface area, pharmacokinetic and toxicity profile of all newly designed O-CH₃ compounds   were   studied   by   Swiss ADME and ADMET lab 2.0 tools. A series of Q1-Q5 out of total 30 compounds fulfilled the criteria for ADME/toxicity profile with high number of hydrogen interactions and exhibited potential inhibition for amino acids of DPP-4. After Docking simulation, SAR study indicated that quercetin derivatives with more hydroxyl substitutions as well as mono methyl substitution (Q1-Q5) showed stronger inhibition. A series Q1-Q5 were observed as the most effective inhibitors in terms of physicochemical, pharmacokinetic, pharmacodynamics, and docking simulation study.

URN:NBN:sciencein.jist.2024.v12.757