Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 400, Issue 1, Pages 169-174Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.08.038
Keywords
1,4-Naphthoquinones; beta-Secretase (BACE); Amyloid aggregation; A beta fibrils; Alzheimer's disease
Categories
Funding
- Chile government [UCN0604]
- [UCM-910815]
- [CTQ2009-14124-C02-01]
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The aim of this study is to find out whether several 1,4-naphthoquinones (1,4-NQ) can interact with the amyloidogenic pathway of the amyloid precursor protein processing, particularly targeting at beta-secretase (BACE), as well as at beta-amyloid peptide (A beta) aggregation and disaggregating preformed A beta fibrils. Compounds bearing hydroxyl groups at the quinoid (2) or benzenoid rings (5,6) as well as some 2- and 3-aryl derivatives (11-15) showed BACE inhibitory activity, without effect on amyloid aggregation or disaggregation. The halogenated compounds 8 and 10 were selective for the inhibition of amyloid aggregation. On the other hand, 1,4-naphthoquinone (1), 6-hydroxy-1,4-naphthoquinone (4) and 2-(3,4-dichlorophenyl)-1,4-naphthoquinone (26) did not show any BACE inhibitory activity but were active on amyloid aggregation and disaggregation preformed A beta fibrils. Juglone (5-hydroxy-1,4-naphthoquinone (3), and 3-(p-hydroxyphenyl)-5-methoxy-1,4-napththoquinone (19) were active on all the three targets. Therefore, we suggest that 1,4-NQ derivatives, specially 3 and 19, should be explored as possible drug candidates or lead compounds for the development of drugs to prevent amyloid aggregation and neurotoxicity in Alzheimer's disease. (C) 2010 Elsevier Inc. All rights reserved.
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