Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment

Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead mol...

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Detalles Bibliográficos
Autores principales: Gupta, Shraddha Manish, Behera, Ashok, Jain, Neetesh K., Tripathi, Avanish, Rishipathak, Dinesh, Singh, Siddharth, Ahemad, Nafees, Erol, Meryem, Kumar, Devendra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476022/
https://www.ncbi.nlm.nih.gov/pubmed/37671344
http://dx.doi.org/10.1039/d3ra03224h
Descripción
Sumario:Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC(50): 4.16 ± 0.063 μM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aβ aggregation at 0.5, 10 and 20 μM doses. Approximately, 50% of AChE-induced Aβ aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.

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