title: In vitro antiamyloidogenic properties of 1,4-naphthoquinones.
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.
authors: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. bescos@farm.ucm.es
authors: Paloma
authors: P
authors: Bermejo-Bescós
authors: Sagrario
authors: S
authors: Martín-Aragón
authors: Karim L
authors: KL
authors: Jiménez-Aliaga
authors: Andrea
authors: A
authors: Ortega
authors: María Teresa
authors: MT
authors: Molina
authors: Eduardo
authors: E
authors: Buxaderas
authors: Guillermo
authors: G
authors: Orellana
authors: Aurelio G
authors: AG
authors: Csákÿ
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D009285:Naphthoquinones; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C035342:1,4-naphthoquinone; C005134:juglone