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

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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
Volume70
Issue number14
DOIs
StatePublished - Jul 8 2005
Externally publishedYes

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Matrix Metalloproteinase 2
Matrix Metalloproteinases
Matrix Metalloproteinase Inhibitors
Biological systems
Acetic Acid
Zinc
Tumors
Ions
Molecules

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Ikejiri, M., Bernardo, M. M., Meroueh, S., Brown, S., Chang, M., Fridman, R., & Mobashery, S. (2005). Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A. Journal of Organic Chemistry, 70(14), 5709-5712. https://doi.org/10.1021/jo050339+

Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A. / Ikejiri, Masahiro; Bernardo, M. Margarida; Meroueh, Samy; Brown, Stephen; Chang, Mayland; Fridman, Rafael; Mobashery, Shahriar.

In: Journal of Organic Chemistry, Vol. 70, No. 14, 08.07.2005, p. 5709-5712.

Research output: Contribution to journalArticle

Ikejiri, M, Bernardo, MM, Meroueh, S, Brown, S, Chang, M, Fridman, R & Mobashery, S 2005, 'Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A', Journal of Organic Chemistry, vol. 70, no. 14, pp. 5709-5712. https://doi.org/10.1021/jo050339+
Ikejiri, Masahiro ; Bernardo, M. Margarida ; Meroueh, Samy ; Brown, Stephen ; Chang, Mayland ; Fridman, Rafael ; Mobashery, Shahriar. / Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A. In: Journal of Organic Chemistry. 2005 ; Vol. 70, No. 14. pp. 5709-5712.
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