Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bmcl.2014.02.006
Title: Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species
Authors: Nguyen, T.
Yang, T.
Go, M.-L. 
Keywords: Acridin-9-yl phenylamines
Glutamate challenge
Mouse hippocampal cells HT22
Neuroprotection
Oxytosis
Radical quenching
Issue Date: 1-Apr-2014
Citation: Nguyen, T., Yang, T., Go, M.-L. (2014-04-01). Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species. Bioorganic and Medicinal Chemistry Letters 24 (7) : 1830-1838. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bmcl.2014.02.006
Abstract: The in vitro neuronal cell death model based on the HT22 mouse hippocampal cell model is a convenient means of identifying compounds that protect against oxidative glutamate toxicity which plays a role in the development of certain neurodegenerative diseases. Functionalized acridin-9-yl-phenylamines were found to protect HT22 cells from glutamate challenge at submicromolar concentrations. The Aryl1-NH-Aryl2 scaffold that is embedded in these compounds was the minimal pharmacophore for activity. Mechanistically, protection against the endogenous oxidative stress generated by glutamate did not involve up-regulation of glutathione levels but attenuation of the late stage increases in mitochondrial ROS and intracellular calcium levels. The NH residue in the pharmacophore played a crucial role in this regard as seen from the loss of neuroprotection when it was structurally modified or replaced. That the same NH was essential for radical scavenging in cell-free and cell-based systems pointed to an antioxidant basis for the neuroprotective activities of these compounds. © 2014 Elsevier Ltd. All rights reserved.
Source Title: Bioorganic and Medicinal Chemistry Letters
URI: http://scholarbank.nus.edu.sg/handle/10635/105972
ISSN: 14643405
DOI: 10.1016/j.bmcl.2014.02.006
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

6
checked on May 17, 2018

WEB OF SCIENCETM
Citations

5
checked on May 9, 2018

Page view(s)

45
checked on Feb 25, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.