In silico evaluation of the antidiabetic potentials of some quercetin derivatives
Keywords:Autodock, diabetes, quercetin, in silico
Background: Quercetin is known to exhibit antidiabetic activity in Type 2 Diabetes mellitus due to its antioxidant property. This study was aimed at designing some derivatives of quercetin and evaluating their binding affinities to target proteins implicated in diabetes mellitus.
Method: Derivatives of quercetin were designed with ChemDraw. The targets: α-amylase (AA), Dipeptidyl peptidase (DPP4); Peroxisome proliferator-activated receptor gamma (PPARG); Glycogen synthase kinases 3β (GSK3); Fructose-1,6-diphosphatase (F16DP); α-glucosidase (AG); Protein Tyrosine Phosphatase 1B (PTP1B); Glucokinase (GK) were downloaded from the Protein data bank. Ligands and targets were converted to pdbqt format using PyRx. Molecular docking of the ligands with each of the target proteins was done using Autodock Vina. Discovery Studio was used to analyse ligand-protein binding interactions. Calculated molecular and pharmacokinetic properties were obtained from molinspiration and pKCM websites, respectively.
Results: Ligands with the best binding affinity on the various targets are AA (ligand 63: -9.2; quercetin: -8.8), AG (ligand 39: -7.9; quercetin: -7.5), DPP4 (ligand 15: -8.8; quercetin: -9.1), PPARG (ligand 23 and 31: -10.3; ligand 15: -10.1; quercetin: -8.8), F16DP (ligand 2, 34, and 47: -6.6; quercetin: -6.2); GSK3 (ligand 15: -8.1; quercetin: -7.9), PTP1B (ligand 26: -9.3; quercetin: -8.9), GK (ligand 37: -9.7; quercetin: -8.7). Ligands that had good binding activity on more than one target are: Ligand 15 (AA, PPARG, and DPP4), Ligand 39 (AA and DPP4), Ligands 25 and 31 (PPARG and PTB1B).
Conclusion: Some of the derivatives had better binding affinity than quercetin on various targets are potential candidates for the treatment of diabetes.
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