title: Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity.
abstract: New catechol-containing chemical entities have been investigated as matrix metalloproteinase inhibitors as well as antioxidant molecules. The combination of the two properties could represent a useful feature due to the potential application in all the pathological processes characterized by increased proteolytic activity and radical oxygen species (ROS) production, such as inflammation and photoaging. A series of catechol-based molecules were synthesized and tested for both proteolytic and oxidative inhibitory activity, and the detailed binding mode was assessed by crystal structure determination of the complex between a catechol derivative and the matrix metalloproteinase-8. Surprisingly, X-ray structure reveals that the catechol oxygens do not coordinates the zinc atom.
authors.affiliation: a Department of Tumor Biology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , FL , USA.
authors.forename: Marilena
authors.initials: M
authors.lastname: Tauro
authors.affiliation: b Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi "A. Moro" di Bari , Bari , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laghezza
authors.affiliation: b Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi "A. Moro" di Bari , Bari , Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
authors.affiliation: b Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi "A. Moro" di Bari , Bari , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Piemontese
authors.affiliation: b Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi "A. Moro" di Bari , Bari , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Caradonna
authors.affiliation: c Istituto di Cristallografia, CNR , Monterotondo Stazione (Roma) , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Capelli
authors.affiliation: c Istituto di Cristallografia, CNR , Monterotondo Stazione (Roma) , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Montanari
authors.affiliation: c Istituto di Cristallografia, CNR , Monterotondo Stazione (Roma) , Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pochetti
authors.affiliation: d Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem , Rehovot , Israel , and.
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Pizio
authors.affiliation: e Dipartimento di Farmacia, Università "G. d'Annunzio" Chieti , Chieti , Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.affiliation: e Dipartimento di Farmacia, Università "G. d'Annunzio" Chieti , Chieti , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campestre
authors.affiliation: b Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi "A. Moro" di Bari , Bari , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000302:isolation & purification / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002396:Catechols; D061965:Matrix Metalloproteinase Inhibitors; D017382:Reactive Oxygen Species; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C034221:catechol
keywords: Antioxidants; X-ray crystallography; inhibitors; metalloenzymes; structure–activity relationships