title: Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity.
abstract: Hydrazide derivatives of Ilomastat, carrying either aryl groups or distinct alkyl and arylsulfonyl moieties were synthesized and evaluated for their MMP inhibitory activity. Potent and selective MMP-9 inhibition (IC(50)=3 nM) was observed for compound 3m (arylsulfonyl group: 4-(4-Br-C6H4)-C6H4-SO(2)-). Interaction with the S2 enzyme subsite is mainly responsible for the inhibitory properties of this derivative as confirmed by molecular docking computation.
authors.affiliation: Université de Reims-Champagne-Ardenne, CNRS UMR 6229, Institut de Chimie Moléculaire de Reims, Faculté de Pharmacie, IFR53 Biomolécules, 51 rue de Cognacq-Jay, 51096 Reims Cedex, France.
authors.forename: Gwennaël
authors.initials: G
authors.lastname: Ledour
authors.forename: Gautier
authors.initials: G
authors.lastname: Moroy
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouffet
authors.forename: Erika
authors.initials: E
authors.lastname: Bourguet
authors.forename: Dominique
authors.initials: D
authors.lastname: Guillaume
authors.forename: Martine
authors.initials: M
authors.lastname: Decarme
authors.forename: Haquima
authors.initials: H
authors.lastname: Elmourabit
authors.forename: Franck
authors.initials: F
authors.lastname: Augé
authors.forename: Alain J P
authors.initials: AJ
authors.lastname: Alix
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Laronze
authors.forename: Georges
authors.initials: G
authors.lastname: Bellon
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Janos
authors.initials: J
authors.lastname: Sapi
mesh_terms: D000465:Algorithms; D001554:Benzene / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D006877:Hydroxamic Acids; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006834:Hydrazines; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013451:Sulfonic Acids; C119203:ilomastat; D001554:Benzene