New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase a (MMP-2)

Armando Rossello, Elisa Nuti, Elisabetta Orlandini, Paolo Carelli, Simona Rapposelli, Marco Macchia, Filippo Minutolo, Laura Carbonaro, Adriana Albini, Roberto Benelli, Giovanni Cercignani, Gillian Murphy, Aldo Balsamo

Research output: Contribution to journalArticlepeer-review

Abstract

New N-arylsulfonyl-substituted alkoxyaminoaceto hydroxamic acid derivatives of types 8 and 10 designed as oxa-analogues of known sulfonamide-based MMPi of types 2 and 7 were synthesized and tested for their inhibitory activities on some matrix metalloproteinases. The combination of a biphenylsulfonamide group with oxyamino oxygen in the pharmacophoric central skeleton of sulfonamide-based MMPi obtained in the new sulfonamides 10 seems to be able to give selectivity for MMP-2 over MMP-1. The most potent derivative of this type, 10a, shows similar anti-invasive properties to the analogue reference drug CGS27023A, 2, in an in vitro model of invasion on matrigel, carried out on cellular lines of fibrosarcoma HT1080 (tumoural cells over-expressing MMP-2 and MMP-9).

Original languageEnglish
Pages (from-to)2441-2450
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number9
DOIs
Publication statusPublished - May 1 2004

Keywords

  • Gelatinase A inhibitors
  • MMP-2 selective
  • Sulfonamide-based MMP inhibitors

ASJC Scopus subject areas

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

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