Unlocking Neurodegeneration: Scaffold-Derived Blockers of MAO-B and AChE inspired by Bryophyllum pinnatum: A Structural Exploration

Abstract

Abstract Alzheimer's disease (AD)and Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping symptoms. Reduced acetylcholine levels in AD are addressed using Acetylcholinesterase (AChE) inhibitors. Monoamine oxidase B (MAO-B) inhibitors prevent dopamine breakdown in PD. Bryophyllum pinnatum, a medicinal plant, that has been used as traditional treatments for various disorders because of its phytochemicals. This study explores its ligands as potential medications for AD and PD by inhibition of AChE and MAO-B. Computer-aided drug design was conducted using Schrödinger Suite software and Maestro 12.8. Ligands from B. pinnatum and standard drugs were docked to the active sites of MAO-B and AChE. ADMET screening and MM/GBSA analysis were performed. Pharmacophore modeling was used to identify compounds matching the reference ligands. After application of all screenings, 4 and 6 hit compounds were found for MAO B & AChE respectively based on good docking score and MM/GBSA as well as good ADMET properties. Pinoresinol was found to be the most potent of the hit compounds. These compounds could be used as neuroprotective agent in near future. Hence, this study provides evidence for consideration of valuable ligands in Bryophyllum pinnatum as potential AChE and MAO-B inhibitors and further in vivo and in vitroinvestigation might prove their therapeutic potential.