Molecular modelling study on Piper betle phytocompounds to discover the potential active moiety responsible for xanthine oxidase inhibition in avian gout.

Abstract

1. This study investigated the phytochemicals responsible for xanthine oxidase (XO) inhibitory activity in Piper betle L. herb. In silico analysis was performed against the active sites of XO using 32 phytocompounds from P. betle along with the known inhibitor allopurinol used in avian gout treatment.2. Functions including docking score and GLIDE score, ADME analyses using QikProp module and toxicity assessment with ProTox-II server. Molecular dynamics simulations were performed for 100 ns with GROMACS software to evaluate the stability and fluctuations of the protein-ligand complexes.3. The results revealed that 12 phytocompounds of P. betle exhibited higher GLIDE XP docking scores (-6.881 to -4.766 kcal/mol) compared to allopurinol (-4.535 kcal/mol) and 11 phytocompounds showed higher GLIDE energy (-42.822 kcal/mol to -36.706 kcal/mol) than allopurinol (-32.676 kcal/mol). Among these, 4-chromanol and 4-allyl-1,2-diacetoxybenzene were identified as the most potent compounds of P. betle, forming hydrogen bond interactions with XO similar to allopurinol.4. The ADME analyses showed that selected phytocompounds met the ADME descriptors and did not violate Lipinski's 'rule of five' and toxicity assessment yielded satisfactory results. Furthermore, 100 ns MD simulations showed a stable trajectory and less conformational variation (RMSD, RMSF) along with a steady interaction profile observed throughout the simulations. The MM‑GBSA calculations supported the docking studies.5. The data showed that 4-chromanol and 4-allyl-1, 2-diacetoxybenzene phytocompounds present in P. betle might account for antigout activity through XO inhibition, meaning that these could be developed as potential drug molecules.