Journal of Bioscience and Biotechnology Discovery

Alzheimer’s disease (AD) and other neurodegenerative disorders are characterized by cholinergic dysfunction, making acetylcholinesterase (AChE) inhibition a therapeutic target. This study investigates the neuroprotective potential of phytoconstituents from Rosmarinus officinalis and Curcuma longa, aiming to identify and evaluate bioactive compounds as potential AChE inhibitors. Ethanolic extracts of R. officinalis and C. longa were analyzed using GC-MS and UHPLC-ESI-Q-TOF-MS/MS to identify key phytoconstituents. Molecular docking simulations were performed using PyRx to assess binding affinities between AChE (PDB ID: 1AMN) and the compounds, including Cycloeicosane, Octacosane, and cis-Vaccenic acid, alongside the standard substrate choline. Drug-likeness, physicochemical properties, lipophilicity, and solubility profiles were predicted using SwissADME, Open Babel for energy minimization, and Silicos-IT for specific solubility and lipophilicity predictions. The docking scores ranged from -6.3 to -7.8 kcal/mol for the identified compounds, significantly outperforming choline (-4.8 kcal/mol). Cycloeicosane exhibited the strongest binding (-7.8 kcal/mol), stabilized by hydrogen, π-sulfur, and multiple alkyl interactions. Physicochemical analysis revealed the hydrophobic nature of most compounds, while cis-Vaccenic acid demonstrated moderate solubility and balanced lipophilicity, enhancing its bioavailability potential. The findings indicate that compounds such as Cycloeicosane and cis-Vaccenic acid are promising AChE inhibitors, offering potential as therapeutic agents for AD. This suggests that the identified phytocompounds could be developed as a novel neuroprotective medication. While computational results are promising, in vitro validation, pharmacokinetic studies, and toxicity assessments are required to confirm their therapeutic efficacy and safety for clinical applications.