In vitro antiamyloidogenic properties of 1,4-naphthoquinones

Paloma Bermejo-Bescós, Sagrario Martín-Aragón, Karim Lizeth Jimenez Aliaga, Andrea Ortega, María Teresa Molina, Eduardo Buxaderas, Guillermo Orellana, Aurelio G. Csákÿ

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41 Scopus citations

Abstract

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 β-secretase (BACE), as well as at β-amyloid peptide (Aβ) aggregation and disaggregating preformed Aβ 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 Aβ 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.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume400
Issue number1
DOIs
StatePublished - Sep 2010
Externally publishedYes

Bibliographical note

Funding Information:
Andrea Ortega is a Ph.D. fellow and is supported by the MECESUP program from the Chile government (UCN0604). Projects UCM-910815 and CTQ2009-14124-C02-01 are gratefully acknowledged for financial support.

Keywords

  • β-Secretase (BACE)
  • 1,4-Naphthoquinones
  • Aβ fibrils
  • Alzheimer's disease
  • Amyloid aggregation

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