Antiamnesic Effects of Novel Phthalimide Derivatives in Scopolamine-Induced Memory Impairment in Mice: A Useful Therapy for Alzheimer's Disease.

Phthalimides have diverse bioactivities and are attractive molecules for drug discovery and development. Here, we explored new synthesized phthalimide derivatives (compounds -) in improving memory impairment associated with Alzheimer's disease (AD), using and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and models, including Y-maze test and novel object recognition test (NORT). Compounds - exhibited significant AChE activity with IC values of 10, 140, and 18 μM and BuChE with IC values of 80, 50, and 11 μM, respectively. All compounds - showed excellent antioxidant potential in DPPH and ABTS assays with IC values in the range of 105-340 and 205-350 μM, respectively. In studies, compounds - also significantly inhibited both enzymes in a concentration-dependent manner along with significant antioxidant activities. In studies, compounds - reversed scopolamine-induced amnesia as indicated by a significant increase in the spontaneous alternation in the Y-maze test and an increase in the discrimination index in the NORT. Molecular docking was also conducted for compounds - against AChE and BuChE, which showed that compounds and have excellent binding with AChE and BuChE as compared to . These findings suggest that compounds - possess significant antiamnesic potential and may serve as useful leads to develop novel therapeutics for the symptomatic management and treatment of AD.