title: N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP.
abstract: Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Pisa, Via Bonanno, 6, 56126 Pisa, Italy. aros@farm.unipi.it
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Paolo
authors.initials: P
authors.lastname: Carelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zandomeneghi
authors.forename: Federica
authors.initials: F
authors.lastname: Balzano
authors.forename: Gloria
authors.initials: G
authors.lastname: Uccello Barretta
authors.forename: Adriana
authors.initials: A
authors.lastname: Albini
authors.forename: Roberto
authors.initials: R
authors.lastname: Benelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cercignani
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
authors.forename: Aldo
authors.initials: A
authors.lastname: Balsamo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001485:Basement Membrane; D018929:Cell Culture Techniques / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases