Molecular Docking-Guided Screening of Phytoconstituents from Artemisia princeps as Allosteric Glucokinase Activators

Abstract

Abstract Background Glucokinase (GK) occurs in pancreatic β-cells and liver cells. GK plays a crucial role in whole-body glucose homeostasis. GK is often referred to as a glucose sensor in the β-cells. Small molecule GK activators not only reduce fasting and basal blood glucose levels but also improve glucose tolerance. Objective The present investigation was proposed to screen some phytoconstituents (from Artemisia princeps) as allosteric activators of the human GK enzyme using in silico molecular docking. Methods A library of phytoconstituents reported in Artemisia princeps was evaluated for the prediction of drug-like properties by in silico approach. Molecular docking studies of the phytoconstituents with GK were performed using AutoDock vina in order to explore binding interactions between the phytoconstituents and GK enzyme followed by in silico prediction of toxicity of these phytoconstituents. Results The selected phytoconstituents showed good pharmacokinetic parameters for oral bioavailability and drug-likeness as contrived by Lipinski’s rule of five. Four compounds (rutin, 5,4'-dihydroxy-6,7,3'-trimethoxyflavone, daucosterol and methyl commate D) showed appreciable binding interactions with the allosteric site residues of the GK enzyme as per docking results. Conclusion These screened phytoconstituents may serve as promising leads for further development of clinically useful and safe allosteric activators of the human GK enzyme.