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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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