title: Sulfonate-containing thiiranes as selective gelatinase inhibitors.
abstract: Matrix metalloproteinases (MMPs) are important zinc-dependent endopeptidases. Two members of this family of enzymes called gelatinases (MMP-2 and MMP-9) have been implicated in a number of human diseases, including cancer, neurological and cardiovascular diseases, and inflammation, to name a few. We describe in this report the preparation and evaluation of two structural types of thiirane inhibitors that show selectivity toward gelatinases. The biphenyl series targets both gelatinases, whereas the monophenyl analogues exhibit potent inhibition of only MMP-2. The latter structural type also exhibits improved water solubility and metabolic stability, both traits desirable for progress of these molecules forward in gelatinase-dependent animal models of disease.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Testero
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Mijoon
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Rachel T
authors.initials: RT
authors.lastname: Staran
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Mana
authors.initials: M
authors.lastname: Espahbodi
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Leticia I
authors.initials: LI
authors.lastname: Llarrull
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Marta
authors.initials: M
authors.lastname: Toth
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
authors.forename: Mayland
authors.initials: M
authors.lastname: Chang
keywords: Slow-binding gelatinase inhibitors; matrix metalloproteinases; thiiranes