Evaluation of Phytochemical Interactions of Syzygium cumini Bark with Xanthine Oxidase, HGPRT, and Adenosine Deaminase: Target Identification, Active Site Prediction, ADMET Analysis and Molecular Docking for Hyperuricemia Management

Abstract

Syzygium cumini (Jamun) is recognized for its rich bioactive profile and potential therapeutic applications, particularly for conditions like hyperuricemia and oxidative stress. This study employs a comprehensive approach to identify and evaluate the pharmacokinetic properties, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics, and toxicological profiles of 13 phytochemicals from S. cumini bark. Target prediction linked several of these compounds to hyperuricemia-related enzyme inhibition. ADMET analysis, along with Lipinski’s rule of five, confirmed their drug-likeness and bioavailability, identifying candidates such as 11-O-galloylbergenin, Betulinic acid, and Gallic acid as promising due to their ability to permeate biological barriers and interact with P-glycoprotein. Molecular docking highlighted notable binding affinities for three key enzymes involved in hyperuricemia: Xanthine oxidase (3NRZ), Hypoxanthine-Guanine Phosphoribosyltransferase (HGPR) (3GGC)), and Adenosine deaminase(1O5R). Specifically, 11-O-galloylbergenin, Ellagitannin, and Canthaxanthin exhibited strong interactions, with binding energies of -10.8 kcal/mol, -9.7 kcal/mol, and -11.1 kcal/mol, respectively. These results suggest their potential as enzyme inhibitors, supporting their development as natural treatments for uric acid-related conditions. Toxicity assessments confirmed that most compounds possess safe profiles, underscoring S. cumini’s value in producing safe, plant-based therapeutics. This work provides a foundation for future research on S. cumini’s bioactive compounds, encouraging further in vivo studies to validate their efficacy and safety for clinical applications.