Abstract / Summary
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by cognitive decline, memory loss, and cholinergic dysfunction [1]. Acetylcholinesterase (AChE) inhibition is still a crucial therapeutic approach, although existing medications like donepezil merely relieve symptoms and have negative side effects [2]. The traditional Ayurvedic Medhya Rasayana plant Convolvulus pluricaulis (Shankhpushpi) has been extensively documented for its neuroprotective and cognitive-enhancing qualities [3, 4]. Tropane alkaloids including convoline, convolidine, convolvine, and confoline are among its phytochemical constituents and provide a viable framework for logical drug design [3]. A targeted library of derivatives based on convolvine was created and assessed as possible AChE inhibitors in this work. Human AChE (PDB ID: 4PQE) was subjected to molecular docking using AutoDock Vina [5], and interactions with important catalytic residues were examined. FT-IR, NMR, and HRMS methods were used to characterise the top-ranked molecule, which was chosen for synthesis based on docking performance. Ellman's colorimetric technique was then used to determine its inhibitory activity [6]. Strong binding affinities were shown by the docking studies, and the chosen molecule outperformed the reference medication and showed advantageous interactions inside the catalytic region. Significant AChE inhibitory action with potency comparable to the standard was confirmed by in vitro assessment. Analysis of the structure–activity relationship revealed that substitution patterns are essential for controlling physicochemical characteristics and binding affinity. These findings identify convolvine-based derivatives as promising scaffolds for the development of novel anti-Alzheimer’s agents, warranting further pharmacological and in vivo validation.