title: Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils.
abstract: BACE1 activity, inhibition of Aβ aggregation, and disaggregation of preformed Aβ fibrils constitute the three major targets in the development of small-molecule lipophilic new drugs for the treatment of Alzheimer's disease (AD). Quinones are widely distributed among natural products and possess relevant and varied biological activities including antitumor and antibiotic, inhibition of HIV-1 reverse transcriptase, antidiabetic, or COX-inhibition, among others. We report herein the interaction of several arylquinones and their derivatives with the amyloidogenic pathway of the amyloid precursor protein processing. Our studies put forward that these compounds are promising candidates in the development of new drugs which are effective simultaneously towards the three major targets of AD.
authors: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, E28040 Madrid, Spain.
authors: Andrea
authors: A
authors: Ortega
authors: Ángela
authors: Á
authors: Rincón
authors: Karim L
authors: KL
authors: Jiménez-Aliaga
authors: Paloma
authors: P
authors: Bermejo-Bescós
authors: Sagrario
authors: S
authors: Martín-Aragón
authors: María Teresa
authors: MT
authors: Molina
authors: Aurelio G
authors: AG
authors: Csákÿ
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000682:Amyloid / Q000737:chemistry*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D011809:Quinones; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human