Neurodegenerative disorders, such as Alzheimer's disease, are characterized by progressive neuronal loss, cognitive decline, and memory impairment, often associated with cholinergic dysfunction. Therapeutic strategies targeting acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) have shown promise in improving cognitive performance. Nostocarboline, a β-carboline alkaloid isolated from freshwater cyanobacteria, has been reported to exhibit inhibitory activity against both AChE and BChE. This study employed an in-silico approach to evaluate Nostocarboline’s potential as a dual cholinesterase inhibitor. Molecular docking simulations were conducted to assess binding affinities, interaction profiles, and stability within enzyme active sites. Molecular dynamics simulations analysed the conformational stability of ligand– enzyme complexes over time. Pharmacokinetic and ADMET analyses evaluated drug-likeness, blood–brain barrier permeability, and toxicity. Results demonstrated strong binding interactions with catalytic and peripheral anionic site residues of both enzymes, favourable stability in dynamic simulations, and acceptable pharmacokinetic properties. These findings suggest that Nostocarboline could serve as a promising lead compound for further development as a dual cholinesterase inhibitor in the management of neurodegenerative disorders, warranting experimental validation.
Chitransh Khare* (Mon,) studied this question.