Inhibition of lysosomal cysteine proteases by a series of Au(I) complexes: a detailed mechanistic investigation

Shamila S Gunatilleke; Amy M Barrios

doi:10.1021/jm060158f

Inhibition of lysosomal cysteine proteases by a series of Au(I) complexes: a detailed mechanistic investigation

J Med Chem. 2006 Jun 29;49(13):3933-7. doi: 10.1021/jm060158f.

Authors

Shamila S Gunatilleke¹, Amy M Barrios

Affiliation

¹ Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA.

PMID: 16789749
DOI: 10.1021/jm060158f

Abstract

Complexes of gold(I) have long been used to treat rheumatoid arthritis although the precise biological targets of gold are not well understood. One intriguing therapeutic target of Au(I) is the cathepsin family of lysosomal cysteine proteases. Here, we present the inhibition of cathepsin B by a known Au(I)-based drug and a series of derivatives. The complexes investigated were reversible, competitive inhibitors with IC50 values ranging from 0.3 to 250 microM, depending on the substituents around the Au(I).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Auranofin / analogs & derivatives
Auranofin / chemical synthesis
Auranofin / chemistry
Cathepsin B / antagonists & inhibitors*
Cathepsin B / chemistry
Chelating Agents / chemical synthesis
Chelating Agents / chemistry
Crystallography, X-Ray
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / chemistry
Kinetics
Ligands
Lysosomes / enzymology*
Organogold Compounds / chemical synthesis*
Phosphines / chemical synthesis
Phosphines / chemistry
Structure-Activity Relationship

Substances

Chelating Agents
Cysteine Proteinase Inhibitors
Ligands
Organogold Compounds
Phosphines
Auranofin
Cathepsin B