In silico docking based screening of constituents from Persian shallot as modulators of human glucokinase.

Abstract

Small molecule glucokinase (GK) modulators not only decrease fasting and basal plasma sugar contents but also progress glucose tolerance. The hydro-ethanolic extract of the Persian shallot (Allium hirtifolium Boiss.) decreased blood glucose, improved plasma insulin and amplified GK action. The present study was proposed to screen phytoconstituents from Persian shallot as human GK activators using in silico docking studies. A total of 91 phytoconstituents reported in Persian shallot (A. hirtifolium Boiss.) were assessed in silico for the prediction of drug-like properties and molecular docking investigations were carried out with human GK using AutoDock vina with the aim of exploring the binding interactions between the phytoconstituents and GK enzyme followed by in silico prediction of toxicity. Almost all the phytoconstituents tested showed good pharmacokinetic parameters for oral bioavailability and drug-likeness. In the docking analysis, cinnamic acid, methyl 3,4,5-trimethoxy benzoate, quercetin, kaempferol, kaempferol 3-O-β-D-glucopyranosyl-(1- > 4)-glucopyranoside, 5-hydroxy-methyl furfural, ethyl N-(O-anisyl) formimidate, 2-pyridinethione and ascorbic acid showed appreciable hydrogen bond and hydrophobic type interactions with the allosteric site residues of the GK enzyme. These screened phytoconstituents may serve as promising hit molecules for further development of clinically beneficial and safe allosteric activators of the human GK enzyme.