In silico study of the anti-xanthine oxidase activity of certain metabolites derived from marine sponges

Abstract

This study investigates the therapeutic potential of five marine-derived metabolites as inhibitors of human xanthine oxidase (HXO), a critical enzymatic target in the treatment of gout an inflammatory disorder caused by the deposition of monosodium urate crystals in joints and surrounding tissues. Two alkaloids, Petrosin (Mol1) and Xestospongin D (Mol2), were selected from the marine sponge Oceanapia sp. A phenolic acid, Gentisic acid (Mol3), was obtained from Hemimycale columella. Additionally, two sesquiterpenoids, Sydonol (Mol4) and Aspergiterpenoid A (Mol5), were derived from a fungal strain (Aspergillus sp.) isolated from the sponge Xestospongia testudinaria. Molecular docking analysis using AutoDock Vina revealed that Mol1 and Mol2 exhibit the strongest binding affinities toward HXO, with binding energies of -11.5 kcal/mol and -8.8 kcal/mol, respectively significantly surpassing the reference drug allopurinol (-5.9 kcal/mol). Mol3, Mol4, and Mol5 also demonstrated enhanced binding stability compared to allopurinol. Complementary ADMT (absorption, distribution, metabolism, and toxicity) predictions indicated favorable pharmacokinetic properties and safety profiles, including low carcinogenic potential and minimal risk for cardiotoxicity. Collectively, these in silico findings underscore the promise of marine-derived metabolites, particularly Mol1 and Mol2, as novel HXO inhibitors that may lead to safer and more effective gout treatments. Further in vitro and in vivo validation is warranted to confirm these results.