title: Inhibition of lysosomal cysteine proteases by a series of Au(I) complexes: a detailed mechanistic investigation.
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).
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Shamila S
authors.initials: SS
authors.lastname: Gunatilleke
authors.forename: Amy M
authors.initials: AM
authors.lastname: Barrios
mesh_terms: D001310:Auranofin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology*; D050607:Organogold Compounds / Q000138:chemical synthesis*; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D015853:Cysteine Proteinase Inhibitors; D008024:Ligands; D050607:Organogold Compounds; D010720:Phosphines; D001310:Auranofin; D002401:Cathepsin B