English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/101864
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Discovery of 5-(4-hydroxyphenyl)-3-oxo-pentanoic acid [2-(5-methoxy-1H- indol-3-yl)-ethyl]-Amide as a neuroprotectant for Alzheimers Disease by Hybridization of Curcumin and Melatonin

AuthorsChojnacki, J.E.; Liu, K.; Yan, X.; Toldo, S.; Selden, T.; Estrada, Martín ; Rodríguez-Franco, María Isabel ; Halquist, M.S.; Ye, D.; Zhang, S.
Issue Date2014
PublisherAmerican Chemical Society
CitationACS Chemical Neuroscience 5: 690- 699 (2014)
AbstractIn our effort to develop effective neuroprotectants as potential treatments for Alzheimer>s disease (AD), hybrid compounds of curcumin and melatonin, two natural products that have been extensively studied in various AD models, were designed, synthesized, and biologically characterized. A lead hybrid compound (7) was discovered to show significant neuroprotection with nanomolar potency (EC50 = 27.60 ± 9.4 nM) in MC65 cells, a cellular AD model. Multiple in vitro assay results established that 7 exhibited moderate inhibitory effects on the production of amyloid-β oligomers (AβOs) in MC65 cells, but not on the aggregation of Aβ species. It also exhibited significant antioxidative properties. Further mechanistic studies demonstrated that 7>s antioxidant effects correlate well with its neuroprotective potency for MC65 cells, and these effects might be due to its interference with the interactions of AβOs within the mitochondria of MC65 cells. Furthermore, 7 was confirmed to cross the blood-brain barrier (BBB) and deliver a sufficient amount to brain tissue after oral administration. Collectively, these results strongly support the hybridization approach as an efficient strategy to help identify novel scaffolds with a desired pharmacology, and strongly encourage further optimization of 7 to develop more potent neuroprotectants for AD.
URIhttp://hdl.handle.net/10261/101864
DOI10.1021/cn500081s
Identifiersdoi: 10.1021/cn500081s
issn: 1948-7193
e-issn: 1948-7193
Appears in Collections:(IQM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.