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Eur J Pharm Sci. 2017 Aug 30;106:393-403. doi: 10.1016/j.ejps.2017.06.028. Epub 2017 Jun 19.

Structural evidence of quercetin multi-target bioactivity: A reverse virtual screening strategy.

Author information

1
Center of Bioinformatics, Faculty of Chemistry, UdelaR, 11800 Montevideo, Uruguay; Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay.
2
Center of Bioinformatics, Faculty of Chemistry, UdelaR, 11800 Montevideo, Uruguay. Electronic address: margot@fq.edu.uy.
3
Department of Sciences, Roma Tre University, 00146 Rome, Italy; National Institute of Nuclear Physics, Roma Tre Section, 00146 Rome, Italy.
4
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay.
5
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.
6
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, Uruguay. Electronic address: jaabin@iibce.edu.uy.

Abstract

The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways. Even though there are a number of well-established protein targets such as phosphatidylinositol 3 kinase and xanthine oxidase, there remains a lack of a comprehensive knowledge of the potential mechanisms of action of quercetin and its target space. In the present work we adopted a reverse screening strategy based on ligand similarity (SHAFTS) and target structure (idTarget, LIBRA) resulting in a set of predicted protein target candidates. Furthermore, using this method we corroborated a broad array of previously experimentally tested candidates among the predicted targets, supporting the suitability of this screening approach. Notably, all of the predicted target candidates belonged to two main protein families, protein kinases and poly [ADP-ribose] polymerases. They also included key proteins involved at different points within the same signaling pathways or within interconnected signaling pathways, supporting a pleiotropic, multilevel and potentially synergistic mechanism of action of quercetin. In this context we highlight the value of quercetin's broad target profile for its therapeutic potential in diseases like inflammation, neurodegeneration and cancer.

KEYWORDS:

Drug target prediction; Flavonoids; Molecular docking; Quercetin

PMID:
28636950
DOI:
10.1016/j.ejps.2017.06.028
[Indexed for MEDLINE]

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