Development of Substituted Benzylidene Derivatives As Novel Dual Cholinesterase Inhibitors for Alzheimer's Treatment

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Sep 6

PMID 37671344

Authors

Shraddha Manish Gupta

Ashok Behera

Neetesh K Jain

Avanish Tripathi

Dinesh Rishipathak

Siddharth Singh

Nafees Ahemad

Meryem Erol

Devendra Kumar

Affiliations

Soon will be listed here.

Abstract

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: 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.

Citing Articles

Potential Azo-8-hydroxyquinoline derivatives as multi-target lead candidates for Alzheimer's disease: An in-depth in silico study of monoamine oxidase and cholinesterase inhibitors.

Guerguer F, Rossafi B, Abchir O, Raouf Y, Albalushi D, Samadi A PLoS One. 2025; 20(1):e0317261.

PMID: 39883631 PMC: 11781659. DOI: 10.1371/journal.pone.0317261.

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