Virtual Screening, Molecular Docking and Pharmacophore Modeling of Phytoconstituents of Flavones as Aldose Reductase Inhibitors

Abstract

Flavones are an important class of naturally occurring heterocycles possessing various pharmacological activities. An in silico approach was carried out where 506 compounds containing flavone ring were utilised as ligand against the target aldose reductase enzyme. Aldose reductase is the rate-limiting enzyme in the polyol pathway, which indirectly causes diabetic complications like diabetic nephropathy and diabetic retinopathy. The flavone containing compounds retrieved from the PubChem were investigated by HTVS (high throughput virtual screening) followed by molecular docking using glide SP and XP docking module in Maestro of Schrodinger software. Among them, the best fifteen compounds were selected for further studies. The binding energy calculation was done using the Prime MM-GBSA module. PASS online prediction tools were used for predicting the antidiabetic activity of the compounds. Also, a pharmacophore model was generated for best interacted fifteen compounds by Phase, which can be used for evaluation of the characteristic features essential for this specific biological activity. The ADMET properties of the compounds were determined using the Qikprop module in the Schrodinger software.