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. © 2010 Elsevier Inc.
|Original language||American English|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 1 Sep 2010|
Bermejo-Bescós, P., Martín-Aragón, S., Jiménez-Aliaga, K. L., Ortega, A., Molina, M. T., Buxaderas, E., Orellana, G., & Csákÿ, A. G. (2010). In vitro antiamyloidogenic properties of 1,4-naphthoquinones. Biochemical and Biophysical Research Communications, 169-174. https://doi.org/10.1016/j.bbrc.2010.08.038