Screening of Newer Phytoconstituents on Novel Enzymes for their Biological Activity

Abstract

Background: Hyperlipidemia and gout are prevalent metabolic disorders significantly impacting global health. The xanthine oxidase and HMG-CoA reductase pathways play pivotal roles in the pathophysiology of these conditions. This study explores the potential of natural phytoconstituents—daidzein, resveratrol, and genistein—as dual inhibitors for these enzymatic targets, offering insights into innovative therapeutic strategies.

Aim: To evaluate the potential of natural phytoconstituents—daidzein, resveratrol, and genistein—as dual inhibitors of xanthine oxidase and HMG-CoA reductase through molecular docking studies and to assess their drug-likeness and pharmacokinetic properties using ADME analysis via SwissADME.

Methodology: The ligands genistein, resveratrol, and daidzein were directed against the enzymes HMG CoA reductase (PDB ID 416A) and xanthine oxidase (PDB ID 1FO4). Version 1.5.6 of the AUTODOCK VINA tool and BIOVIA Discovery Studio were used for docking simulations. Analysis was done on all of the protein sequences' amino acid residues and hydrogen bonding interactions. Following the docking method, the phytochemicals were further evaluated utilizing the SwissADME ONLINE program for insilico ADME analysis and drug-like prediction. TSPA (topological polar surface area) and miLogP (molinspiration log P) values were used to test for drug-likeness characteristics. Result Xanthine oxidase produced the best docking simulations with Daidzein (-8.7 kcal/mol), Genistein (-8.4 kcal/mol), and Resveratrol (-7.4 kcal/mol). Similarly, when HMG CoA reductase was the target, Genistein (-8.4 kcal/mol), Daidzein (-7.8 kcal/mol), and Resveratrol (-7.7 kcal/mol) had the best docking scores. Certain phytoconstituents adhere to the drug likeness Log P values and ADME limitations.

Conclusion: The molecular docking studies revealed that daidzein, resveratrol, and genistein exhibit strong binding affinities towards xanthine oxidase and HMG-CoA reductase, suggesting their potential as dual inhibitors for managing hyperlipidemia and gout. ADME analysis further confirmed their favorable drug-likeness and pharmacokinetic profiles, highlighting their viability as promising candidates for therapeutic development.