In vitro antiamyloidogenic properties of 1,4-naphthoquinones |
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Authors: | Paloma Bermejo-Bescós Sagrario Martín-Aragón Andrea Ortega Eduardo Buxaderas Aurelio G Csákÿ |
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Institution: | a Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Spain b Instituto de Química Médica (CSIC), Madrid, Spain c Departamento de Química Orgánica, Facultad de Química, Universidad Complutense de Madrid, Spain |
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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. |
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Keywords: | 1 4-Naphthoquinones β-Secretase (BACE) Amyloid aggregation Aβ fibrils Alzheimer&rsquo s disease |
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