Quercetin as a multitarget inhibitor: poor selectivity or something else?

CONTI, GERMÁN ANDRES; PEREZ, ERNESTO RAFAEL; ANGELINA, EMILIO LUIS; GÓMEZ CHÁVEZ JOSÉ LEONARDO; PERUCHENA, NÉLIDA MARÍA

Corrientes

Congreso; XII CAB2C Congreso Argentino de Bioinformática y Biología Computacional; 2022

Asociación Argentina de Bioinformática y Biología Computacional

Background: Quercetin (QUE) is a naturally occurring phytochemical with several proven biologicaleffects, including anticancer, antidiabetic, antiinflammatory, antioxidant, anti-Aging, antimicrobial,anti-Alzheimer’s, antiarthritic, cardiovascular, and wound-healing effects. QUE excerpts those benefits by directly targeting key enzymes involved in several biological pathways. QUE can inhibit kinases, proteases, glucosidases, endopeptidases, hydrolases, topoisomerases, among others. A question that arises is: What makes QUE so versatile as to be able to bind and block such a diversity of molecular targets?Results: To answer the above question we performed a structural survey with cheminformatic tools of QUE-enzyme complexes deposited on the Protein Data Bank (PDB). Alignment of all the QUE-enzyme complexes by the QUE atoms allowed the characterization of the environment of each QUE atom within the protein context. The extracted atomic environments were fed into cheminformatic and machine learning algorithms to expose the common pharmacophoric features that allow binding to all the different protein targets.Conclusions: Analysis of QUE atomic environments provided some clues about a common enzymeinhibition mechanism by this flavonoid. Atomic environments could be also used to predict novelprotein targets of QUE.