IN-SILICO EVALUATION OF ROSIGLITAZONE PRODRUG AGAINST NEURODEGENERATIVE DISEASE
Abstract
Introduction: This study explores the molecular interactions and pharmacokinetic properties of a prodrug, rosiglitazone their potential as therapeutic agents. Material and Methods: Molecular docking was conducted using AutoDock Vina, with the prodrug showing the strongest binding affinity (-10.5 kcal/mol) compared to rosiglitazone (-10.2 kcal/mol) and the co-crystallized ligand (-9.4 kcal/mol). Result and Discussion: Detailed interaction analysis revealed that the prodrug forms multiple hydrogen bonds and π-π interactions, particularly with Trp286 and His447, highlighting its strong binding capacity. Rosiglitazone demonstrated similar interactions, though with fewer bonding sites. Absorption, distribution, metabolism, and excretion (ADME) profiling was performed to assess pharmacokinetic properties using Swiss ADME. The prodrug and rosiglitazone exhibited high gastrointestinal absorption but were not permeant to the blood-brain barrier (BBB). In contrast, reticuline was found to cross the BBB, making it a strong candidate for central nervous system (CNS) applications. Reticuline, however, is a P-glycoprotein (Pgp) substrate, which may affect its bioavailability due to efflux transport mechanisms. All compounds showed no violations of Lipinski’s rules, indicating favorable drug-like properties, with a bioavailability score of 0.55. Conclusion: The study concludes that the prodrug, with its superior binding affinity and favorable ADME properties, holds significant promise for systemic therapies, while reticuline’s BBB permeability makes it a potential candidate for CNS-targeted treatments. Further research is warranted to optimize their clinical applications.
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