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

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