Abstract
Phthalimides have diverse bioactivities and are attractive molecules for drug discovery and development. Here, we explored new synthesized phthalimide derivatives (compounds
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) 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
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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
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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
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also significantly inhibited both enzymes in a concentration-dependent manner along with significant antioxidant activities. In
studies, compounds
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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
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against AChE and BuChE, which showed that compounds
and
have excellent binding with AChE and BuChE as compared to
. These findings suggest that compounds
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possess significant antiamnesic potential and may serve as useful leads to develop novel therapeutics for the symptomatic management and treatment of AD.