Integrated <i>in silico</i> – <i>in vitro</i> strategy for the discovery of potential xanthine oxidase inhibitors from Egyptian propolis and their synergistic effect with allopurinol and febuxostat
Dina S. Ghallab, Eman Shawky, Ali Metwally, İsmail Çeli̇k, Reham S. Ibrahim, Mohamed M. Mohyeldin
Abstract
XO inhibitory assays demonstrated the ability of these hits to significantly inhibit XO in a dose-dependent manner. Molecular docking and MD simulations revealed a cooperative binding mode between the discovered hits and standard XO inhibitors within the active site. Subsequently, the most promising hits were tested in a fixed-ratio combination setting with allopurinol and febuxostat separately to assess their combined effects on XO catalytic inhibition. The binary combination of each techtochrysin and rosmarinic acid with febuxostat displayed maximal synergy at lower effect levels. In contrast, individually, techtochrysin and rosmarinic acid with allopurinol cooperated synergistically at high dose levels. Taken together, the suggested strategy seems imperative to ensure a steady supply of new therapeutic options sourced from Egyptian propolis to regress the development of hyperuricemia.