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

Bioorg Med Chem. 2004 May 1;12(9):2441-50. doi: 10.1016/j.bmc.2004.01.047.

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).

MeSH terms

  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase Inhibitors*
  • Protease Inhibitors / pharmacology*

Substances

  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Matrix Metalloproteinase 2