Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer’s: Design, Synthesis, and Biological Evaluation

Loading...
Thumbnail Image
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Date
2023-01
Major/Subject
Mcode
Degree programme
Language
en
Pages
11
Series
PHARMACEUTICS, Volume 15, issue 1
Abstract
As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer’s disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additionally, compared with donepezil as the standard drug, these Indene analogs were accessed for their cell line-based toxicity study on SH-SY5Y cell line. The molecule SD-30, having hydrogen bond donor (HBD) at para-position, showed maximum AChE inhibition potential (IC50 13.86 ± 0.163 µM) in the indene series. Further, the SD-30 showed maximum BuChE inhibition potential (IC50 = 48.55 ± 0.136 µM) with a selectivity ratio of 3.50 and reasonable antioxidant properties compared to ascorbic acid (using DPPH assay). SD-30 (at a dose level: of 10 µM, 20 µM) effectively inhibited AChE-induced Aβ aggregation and showed no significant toxicity up to 30 mM against SH-SY5Y cell lines.
Description
Publisher Copyright: © 2022 by the authors.
Keywords
acetylcholinesterase, ADMET screening, Alzheimer’s disease, donepezil, fused ring scaffolds, hyrazide conjugation, indene-hydrazide conjugates, SH-SY5Y cell line
Other note
Citation
Gupta , S M , Behera , A , Jain , N K , Kumar , D , Tripathi , A , Tripathi , S M , Mujwar , S , Patra , J & Negi , A 2023 , ' Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer’s: Design, Synthesis, and Biological Evaluation ' , PHARMACEUTICS , vol. 15 , no. 1 , 94 . https://doi.org/10.3390/pharmaceutics15010094