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

Shraddha Manish Gupta, Ashok Behera, Neetesh K. Jain, Avanish Tripathi, Dinesh Rishipathak, Siddharth Singh, Nafees Ahemad, Meryem Erol, Devendra Kumar

Research output: Contribution to journalArticleResearchpeer-review

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 (IC50: 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.

Original languageEnglish
Pages (from-to)26344-26356
Number of pages13
JournalRSC Advances
Volume13
Issue number38
DOIs
Publication statusPublished - 4 Sept 2023

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