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.
