title: From sensors to silencers: quinoline- and benzimidazole-sulfonamides as inhibitors for zinc proteases.
abstract: Derived from the extensive work in the area of small molecule zinc(II) ion sensors, chelating fragment libraries of quinoline- and benzimidazole-sulfonamides have been prepared and screened against several different zinc(II)-dependent matrix metalloproteinases (MMPs). The fragments show impressive inhibition of these metalloenzymes and preferences for different MMPs based on the nature of the chelating group. The findings show that focused chelator libraries are a powerful strategy for the discovery of lead fragments for metalloprotein inhibition.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouffet
authors.forename: César Augusto F
authors.initials: CA
authors.lastname: de Oliveira
authors.forename: Yael
authors.initials: Y
authors.lastname: Udi
authors.forename: Arpita
authors.initials: A
authors.lastname: Agrawal
authors.forename: Irit
authors.initials: I
authors.lastname: Sagi
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Seth M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D055808:Drug Discovery; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011804:Quinolines; D013449:Sulfonamides; C031000:benzimidazole; C037219:quinoline; D020782:Matrix Metalloproteinases; D015032:Zinc