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

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.

Computational Design of Plant‐Based Antistress Agents Targeting Nociceptin Receptor

“…These plants are traditionally used to get relief from stressful conditions and are previously stated in the literature for the same cause [48–51] . Thus, these diverse ligands from herbal source were considered in the molecular library with intent to recognize the most optimized lead responsible for the generation of antistress effect in humans as well as establishing the likely physiological mechanism involved in the stress relieving effect of that particular active ingredient from these plants [52–54] …”

A Network Pharmacology Study of the Active Components of Fufang Huangbai Ye for the Treatment of Ulcerative Colitis

“…[28][29][30][31][32][33] AutoDock Tools software was used to identify active binding pockets within the macromolecular target and used to prepare the imaginary grid box. [34][35][36][37][38] The grid parameters used in the current study were tabulated in table 1.…”

“…Molecular docking based computational screening were performed by using AutoDock 4.2 software of the prepared ligand library against the predicted therapeutic targets for ulcerative colitis [28–33] . AutoDock Tools software was used to identify active binding pockets within the macromolecular target and used to prepare the imaginary grid box [34–38] . The grid parameters used in the current study were tabulated in table 1.…”

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

“… 9 Thus, the library of the indene analogs was prepared and detailed in silico analysis was reported in our previous publication. 10 Further, our next publication reported the in vitro analysis of the indene methylene analogues. 11 The encouraging results in these studies showed indene nucleus attached to the linker, substituent and tailing group are vital for the activity.…”

“… 10 Further, our next publication reported the in vitro analysis of the indene methylene analogues. 11 The encouraging results in these studies showed indene nucleus attached to the linker, substituent and tailing group are vital for the activity. Hydroxy substitution at para and ortho positions was found to be most active against AChE.…”