Probing the potential of platinum(II) complexes for the inhibition of thiol-dependent enzymatic activity.
The synthesis and biological evaluation of platinum(II) amine complexes designed to act as inhibitors of the human cysteine protease cathepsin B, a thiol-dependent enzyme, is described. The complexes, composed of a cathepsin targeting ligand and a platinum(II) moiety with varying degrees of reactivity towards nucleophiles were characterized by physical-analytical methods and a proof of principle was illustrated in a model reaction. In biological tests for inhibitory activity against cathepsin B the presented compounds did not show significant inhibitory activity.
van Zutphen
Steven
S
Leiden Institute of Chemistry, Gorlaeus Laboratories,Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Kraus
Marianne
M
Driessen
Christoph
C
van der Marel
Gijs A
GA
Overkleeft
Herman S
HS
Reedijk
Jan
J
D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D015853:Cysteine Proteinase Inhibitors; D008024:Ligands; D009944:Organoplatinum Compounds; D002401:Cathepsin B