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Anticholinesterase Activities of Novel Isoindolin-1,3-Dione-Based Acetohydrazide Derivatives: Design, Synthesis, Biological Evaluation, Molecular Dynamic Study Publisher

Summary: Can new compounds help Alzheimer’s? A study found isoindolin-based molecules strongly inhibit brain enzymes, showing potential for Alzheimer’s treatment. #AlzheimersResearch #DrugDiscovery

Nazarian A1 ; Abedinifar F1 ; Hamedifar H2, 3 ; Hashempur MH4 ; Mahdavi M1 ; Sepehri N2, 3 ; Iraji A4, 5
Authors

Source: BMC Chemistry Published:2024


Abstract

In pursuit of developing novel cholinesterase (ChE) inhibitors through molecular hybridization theory, a novel series of isoindolin-1,3-dione-based acetohydrazides (compounds 8a–h) was designed, synthesized, and evaluated as possible acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. In vitro results revealed IC50 values ranging from 0.11 ± 0.05 to 0.86 ± 0.02 µM against AChE and 5.7 ± 0.2 to 30.2 ± 2.8 µM against BChE. A kinetic study was conducted on the most potent compound, 8a, to ascertain its mode of inhibition, revealing its competitive mode against AChE. Furthermore, the binding interaction modes of the most active compound within the AChE active site was elucidated. Molecular dynamics simulations of compound 8a were performed to assess the stability of the 8a-AChE complex. In silico pharmacokinetic predictions for the most potent compounds indicated their potential as promising lead structure for the development of new anti-Alzheimer’s disease (anti-AD) agents. © The Author(s) 2024.
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