Phytocompounds of Senecio candicans as potential acetylcholinesterase inhibitors targeting Alzheimer's disease: A structure-based virtual screening and molecular dynamics simulation study

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline due to the accumulation of amyloid-beta plaques, neurofibrillary tangles, and decreased acetylcholine levels caused by acetylcholinesterase (AChE) activity. Current treatments using synthetic acetylcholinesterase inhibitors (AChEIs) provide only symptomatic relief and are associated with adverse effects, highlighting the need for safer and more effective alternatives. This study investigates the potential of phytoconstituents from the plant Senecio candicans as natural AChE inhibitors for AD treatment. Using structure-based virtual screening, molecular docking, and molecular dynamics simulations, we evaluated several compounds from Senecio candicans for their binding affinity, stability, and inhibitory activity against AChE. The findings identified compounds such as Estra-135(10)-trien-17β-ol and Vulgarone A, which demonstrated strong binding affinities and stable interactions with AChE, comparable to or surpassing the clinically used drug Donepezil. These phytoconstituents exhibited potential as effective AChEIs with potentially fewer side effects. The results underscore the therapeutic potential of plant-based molecules for drug discovery, offering a promising avenue for developing new treatments for neurodegenerative diseases. Combining phytochemical studies with computational methods provides a powerful approach to identifying novel therapeutic agents. This study suggests that phytoconstituents from Senecio candicans could serve as safer alternatives for managing AD. Further experimental validation and clinical studies are necessary to confirm these compounds' efficacy and safety, paving the way for innovative, plant-derived treatments for Alzheimer's disease.