title: New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2).
abstract: New N-arylsulfonyl-substituted alkoxyaminoaceto hydroxamic acid derivatives of types 8 and 10 designed as oxa-analogues of known sulfonamide-based MMPi of types 2 and 7 were synthesized and tested for their inhibitory activities on some matrix metalloproteinases. The combination of a biphenylsulfonamide group with oxyamino oxygen in the pharmacophoric central skeleton of sulfonamide-based MMPi obtained in the new sulfonamides 10 seems to be able to give selectivity for MMP-2 over MMP-1. The most potent derivative of this type, 10a, shows similar anti-invasive properties to the analogue reference drug CGS27023A, 2, in an in vitro model of invasion on matrigel, carried out on cellular lines of fibrosarcoma HT1080 (tumoural cells over-expressing MMP-2 and MMP-9).
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: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Paolo
authors.initials: P
authors.lastname: Carelli
authors.forename: Simona
authors.initials: S
authors.lastname: Rapposelli
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.forename: Laura
authors.initials: L
authors.lastname: Carbonaro
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: D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020778:Matrix Metalloproteinase 2