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

Andrea Ortega, Ángela Rincón, Karim L. Jiménez-Aliaga, Paloma Bermejo-Bescós, Sagrario Martín-Aragón, María Teresa Molina, Aurelio G. Csákÿ

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)2183-2187
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number8
DOIs
StatePublished - 15 Apr 2011

Bibliographical note

Funding Information:
Andrea Ortega (PhD fellow) thanks the government of Chile and the ‘Universidad Católica del Norte’ (Antofagasta, Chile) for a grant (MECESUP program, UCN0604). Projects CTQ2009-14124-C02-01, CTQ2010-16170 and SAF2009-10399 from the Spanish government are gratefully acknowledged for financial support.

Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.

Keywords

  • Alzheimer's disease
  • Amyloid aggregation
  • Aβ fibrils
  • BACE1
  • Quinones

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