Abstract
A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.
Highlights
Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by progressive decline of memory and cognition [1]
As a part of our ongoing research project aimed at identifying potential cholinesterase inhibitors for AD therapy [23,24,25,26,27,28,29,30,31,32,33], we report here our efforts in search of novel potent cholinesterase inhibitors using dipolar cycloaddition strategy
Molecular modeling studies were performed to disclose the binding modes of the most active inhibitors to the amino acid residues that compose the active site of the AChE enzyme
Summary
Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by progressive decline of memory and cognition [1]. The increasing mortality rate and the reduced therapeutic potential of the currently available options have led us to focus our research activities on the development of potential cholinesterase inhibitors for the treatment of AD. Ionic liquids are widely recognized as “green” solvents in organic synthesis because of their unique properties, such as low vapor pressure, high chemical and thermal stability, solvating ability, non-flammability, behavior as acidic or basic catalysts and recyclability [10,11,12,13,14]. In this context, ionic liquids have emerged as new green solvents to replace the volatile organic compounds and they are found suitable for executing many diverse organic reactions [15,16,17]. Molecular modeling studies were performed to disclose the binding modes of the most active inhibitors to the amino acid residues that compose the active site of the AChE enzyme
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