N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

Armando Rossello, Elisa Nuti, Paolo Carelli, Elisabetta Orlandini, Marco Macchia, Susanna Nencetti, Maurizio Zandomeneghi, Federica Balzano, Gloria Uccello Barretta, Adriana Albini, Roberto Benelli, Giovanni Cercignani, Gillian Murphy, Aldo Balsamo

Research output: Contribution to journalArticlepeer-review

Abstract

Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R 2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.

Original languageEnglish
Pages (from-to)1321-1326
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number5
DOIs
Publication statusPublished - Mar 1 2005

Keywords

  • Antiangiogenic agents
  • MMP-2/MT1-MMP selective inhibitors
  • MMP-inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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