Virtual screening, ADME study, and molecular dynamic simulation of chalcone and flavone derivatives as 5-Lipoxygenase (5-LO) inhibitor

Abstract

ABSTRACT5-Lipoxygenase (5-LO) is one of the key enzymes involved in the production of pro-inflammatory mediators, such as leukotriene B4 and cysteinyl leukotrienes. Inhibition of 5-LO is a promising therapeutic strategy against inflammation. Chalcones and flavones are known to have a broad spectrum of biological activities which include anti-inflammation, anti-fungal, anti-cancer, and anti-oxidant properties. In this work, computational approaches were used to screen chalcone and flavone derivatives for their potential as inhibitors of 5-LO. The scaffolds for chalcone and flavones were designed and used to select only chalcone and flavone compounds from the ASINEX database. Prior to docking, chalcone and flavone derivatives were filtered using Lipinski’s rule of five (ro5). The top-ranked hits from GLIDE were re-docked using GOLD software to validate the binding mode of the compounds which were screened. Six compounds were selected for further analysis for ADME properties, followed by molecular dynamic (MD) simulations in order to investigate binding interactions. Compound 6 (BAS00795786) had the highest potential as an inhibitor of 5-LO among the selected compounds.