title: Probing the potential of platinum(II) complexes for the inhibition of thiol-dependent enzymatic activity.
abstract: 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.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories,Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: van Zutphen
authors.forename: Marianne
authors.initials: M
authors.lastname: Kraus
authors.forename: Christoph
authors.initials: C
authors.lastname: Driessen
authors.forename: Gijs A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: 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*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D008024:Ligands; D009944:Organoplatinum Compounds; D002401:Cathepsin B