In silico Molecular Docking Analysis of Bioactive Phytoconstituents against Environmental Neurotoxin Bisphenol-A.
Abstract
INTRODUCTION Cognitive impairment, also commonly referred to as intellectual disability, is a complex disorder that affects a person's ability to think, remember, and learn. Bisphenol A is an environmental toxicant that has detrimental effects on the nervous system's functioning over prolonged periods. Bioactive phytochemicals are a viable choice for promoting cognitive health in ageing populations, as they are widely available, reasonably priced, and generally have fewer adverse effects than synthetic medications.
Methods
The in silico study was designed to predict the binding potential of bioactive phytoconstituents, viz. caffeic acid, chlorogenic acid, ferulic acid, and picroside II, against various selected targets. ΔG and ADMET predictions were carried out to determine physicochemical parameters and drug-likeness. 2D and 3D structural analysis, along with bioavailability radar and the boiled egg model, was conducted to study the bioavailability of selected ligands.
Results
Molecular docking study conducted on eight different molecular targets with a G score of -5.5 to -10.3 kcal/mol, indicating the ligands with the highest predicted binding affinity (picroside II > chlorogenic acid > caffeic acid > ferulic acid). ΔG, ADMET showed BPA as a toxicant with the best molecular docking at COX-2, IL-2, IL-12, and LC3B targets.
Discussion
As a protagonist against BPA, chlorogenic acid and picroside II showed similar molecular docking. The bioavailability radar and boiled egg model showed poor bioavailability of chlorogenic acid and picroside II as compared to caffeic acid and ferulic acid. Overall, the compounds represented a desirable ADMET profile (caffeic acid > ferulic acid > chlorogenic acid > picroside II).
Conclusion
This study has enabled the development of future biocompatible and multi-target bioactive phytoconstituents for treating complex nervous system diseases like cognitive impairment, where targeting multiple pathways simultaneously can improve therapeutic outcomes.