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

doi:10.1016/j.bmcl.2011.03.023

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

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33 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 language	English
Pages (from-to)	2183-2187
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.03.023
State	Published - 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.

Keywords

Alzheimer's disease
Amyloid aggregation
Aβ fibrils
BACE1
Quinones

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Ortega, A., Rincón, Á., Jiménez-Aliaga, K. L., Bermejo-Bescós, P., Martín-Aragón, S., Molina, M. T., & Csákÿ, A. G. (2011). Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils. Bioorganic and Medicinal Chemistry Letters, 21(8), 2183-2187. https://doi.org/10.1016/j.bmcl.2011.03.023

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Ortega, A, Rincón, Á, Jiménez-Aliaga, KL, Bermejo-Bescós, P, Martín-Aragón, S, Molina, MT & Csákÿ, AG 2011, 'Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 8, pp. 2183-2187. https://doi.org/10.1016/j.bmcl.2011.03.023

Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils. / Ortega, Andrea; Rincón, Ángela; Jiménez-Aliaga, Karim L. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 8, 15.04.2011, p. 2183-2187.

Research output: Contribution to journal › Article › peer-review

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AU - Bermejo-Bescós, Paloma

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

Abstract

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Keywords

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