title: Natural occurring polyphenols as template for drug design. Focus on serine proteases.
abstract: Several major physio-pathological processes, including cancer, inflammatory states and thrombosis, are all strongly dependent upon the fine regulation of proteolytic enzyme activities, and dramatic are the consequences of unbalanced equilibria between enzymes and their cognate inhibitors. In this perspective, the discovery of small-molecule ligands able to modulate catalytic activities has a massive therapeutic potential and is a stimulating goal. Numerous recent experimental evidences revealed that proteolytic enzymes can be opportunely targeted, reporting on small ligands capable of binding to these biological macromolecules with drug-like potencies, and primarily with comparable (or even higher) efficiency with respect to their endogenous binding partner. In particular, natural occurring polyphenols and their derivatives recently disclosed these intriguing abilities, making them promising templates for drug design and development. In this review, we compared the inhibitory capacities of a set of monomeric polyphenols toward serine proteases activity, and finally summarized the data with an emphasis on the derivation of a pharmacophore model.
authors.affiliation: Department of Molecular, Cellular and Animal Biology, University of Camerino, Via Gentile III da Varano, Camerino (MC), Italy. massimiliano.cuccioloni@unicam.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.forename: Matteo
authors.initials: M
authors.lastname: Mozzicafreddo
authors.forename: Laura
authors.initials: L
authors.lastname: Bonfili
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eleuteri
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
mesh_terms: D020134:Catalytic Domain; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D059808:Polyphenols; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D015842:Serine Proteinase Inhibitors; D054852:Small Molecule Libraries; D012697:Serine Endopeptidases