Structural evidence of quercetin multi-target bioactivity

A reverse virtual screening strategy

Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J Williams, Juan A. Abin-Carriquiry

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)393-403
Number of pages11
JournalEuropean Journal of Pharmaceutical Sciences
Volume106
DOIs
Publication statusPublished - 19 Jun 2017

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Quercetin
Proteins
Phosphatidylinositol 3-Kinase
Poly(ADP-ribose) Polymerases
Xanthine Oxidase
Flavonoids
Protein Kinases
Action Potentials
Neoplasms
Oxidative Stress
Anti-Inflammatory Agents
Antioxidants
Pathology
Ligands
Inflammation
Health
Therapeutics

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Structural evidence of quercetin multi-target bioactivity : A reverse virtual screening strategy. / Carvalho, Diego; Paulino, Margot; Polticelli, Fabio; Arredondo, Florencia; Williams, Robert J; Abin-Carriquiry, Juan A.

In: European Journal of Pharmaceutical Sciences, Vol. 106, 19.06.2017, p. 393-403.

Research output: Contribution to journalArticle

Carvalho, Diego ; Paulino, Margot ; Polticelli, Fabio ; Arredondo, Florencia ; Williams, Robert J ; Abin-Carriquiry, Juan A. / Structural evidence of quercetin multi-target bioactivity : A reverse virtual screening strategy. In: European Journal of Pharmaceutical Sciences. 2017 ; Vol. 106. pp. 393-403.
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