期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 23, 期 5, 页码 1232-1237出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.01.013
关键词
Neuroprotective agents; Na+/K+-ATPase pump; Stroke; Oxidative damage; Natural products
资金
- National Institutes of Health [R00AT004197]
Stroke is a debilitating disease and the third leading cause of death in the USA, where over 2000 new stroke cases are diagnosed every day. Treatment options for stroke-related brain damage are very limited and there is an urgent need for effective neuroprotective agents to treat these conditions. Comparison of the structures of several classes of neuroprotective natural products such as limonoids and cardiac glycosides revealed the presence of a common structural motif which may account for their observed neuroprotective activity. Several natural product mimics that incorporate this shared structural motif were synthesized and were found to possess significant neuroprotective activity. These compounds enhanced cell viability against H2O2 induced oxidative stress or cell death in PC12 neuronal cells. The compounds were also found to enhance and modulate Na+/K+-ATPase activity of PC12 cells, which may suggest that the observed neuroprotective activity is mediated, at least partly, through interaction with Na+/K+-ATPase. (c) 2013 Elsevier Ltd. All rights reserved.
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