Improved gelatinase a selectivity by novel zinc binding groups containing galardin derivatives.
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.
UMR 6013 'Isolement, Structure, Transformation et Synthèse de Produits Naturelles', Faculté de Pharmacie, IFR53 Biomolécules, Université de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, France.
Franck
F
Augé
William
W
Hornebeck
Martine
M
Decarme
Jean-Yves
JY
Laronze
D001665:Binding Sites; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
D004151:Dipeptides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D015032:Zinc