Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives

Bioorg Med Chem Lett. 2003 May 19;13(10):1783-6. doi: 10.1016/s0960-894x(03)00214-2.

Abstract

The synthesis of several analogues of galardin, a MMP inhibitor, are presented with their in vitro inhibitory activity against MMP-1 and MMP-2. These compounds contain a distinct Zinc Binding Group (ZBG). Those having a 2-acylated-heterocycle as well as a 2-arylamide function do not exhibit a good inhibition/selectivity against the enzymes tested. On the contrary, those that are based on a hydrazide scaffold present potent selectivity for MMP-2 versus MMP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Dipeptides / chemical synthesis*
  • Dipeptides / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase Inhibitors*
  • Models, Molecular
  • Structure-Activity Relationship
  • Zinc / chemistry

Substances

  • Dipeptides
  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Zinc