Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils

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• 作者：Andrea Ortega^a ; Á ; ngela Rinc&#xf3 ; n^b ; Karim L. Jimé ; nez-Aliaga^a ; Paloma Bermejo-Besc&#xf3 ; s^a ; ^{bescos@farm.ucm.es} ; Sagrario Martí ; n-Arag&#xf3 ; n^a ; Marí ; a Teresa Molina^c ; Aurelio G. Csá ; k&#xff ; ^b ; ^{csaky@quim.ucm.es}
• 关键词：Alzheimer’ ; s disease ; BACE1 ; Aβ ; fibrils ; Amyloid aggregation ; Quinones
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 April 2011
• 年：2011
• 卷：21
• 期：8
• 页码：2183-2187
• 全文大小：273 K

文摘

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.