title: Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids.
abstract: Metalloproteases are a family of zinc-containing endopeptidases involved in a variety of pathological disorders. The use of flavonoid derivatives as potential metalloprotease inhibitors has recently increased.Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin, apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside, and 7-O-glucuronide).The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized correlatingin vitrotarget-oriented screening andin silicodocking.The flavones apigenin, luteolin, and their respective glucosides have good ability to interact with metalloproteases and can also be lead compounds for further development. Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1, MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring to the active site of MMP-1, -3, -8, -9, and -13. Overall, thein silicodata are substantially in agreement with thein vitroones (fluorimetric assay).
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Crascì
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Basile
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Panico
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Puglia
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Bonina
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Pierluigi Maria
authors.initials: PM
authors.lastname: Basile
authors.affiliation: Bionap s. r. l., Contrada Fureria, Belpasso, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rizza
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guccione
mesh_terms: D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005419:Flavonoids / Q000494:pharmacology*; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020782:Matrix Metalloproteinases; D062105:Molecular Docking Simulation
chemical_list: D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D047310:Apigenin; D020782:Matrix Metalloproteinases; D047311:Luteolin