Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A

Masahiro Ikejiri, M. Margarida Bernardo, Samy O. Meroueh, Stephen Brown, Mayland Chang, Rafael Fridman, Shahriar Mobashery

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Matrix metalloproteinases (MMPs), of which 26 are known, have been implicated in a number of pathological conditions, including tumor metastasis. We have previously described the first mechanism-based inhibitor for MMPs (J. Am. Chem. Soc. 2000, 122, 6799-6800), which in chemistry mediated by the active site zinc ion selectively and covalently inhibits MMP-2, -3, and -9. Computational analyses indicated that this selectivity in inhibition of MMPs could be improved by design of new variants of the inhibitor class. We report herein the syntheses of methyl 2-(4-{4-[(2-thiiranylpropyl)-sulfonyl]phenoxy} phenyl)acetate (3) and 2-(4-{4-[(2-thiiranylpropyl)sulfonyl]phenoxy}phenyl) acetic acid (4), and show that compound 3 serves as a mechanism-based inhibitor exclusively for MMP-2. This molecule should prove useful in delineating the functions of MMP-2 in biological systems.

Original languageEnglish (US)
Pages (from-to)5709-5712
Number of pages4
JournalJournal of Organic Chemistry
Issue number14
StatePublished - Jul 8 2005
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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