Tuning the Au(I)-mediated inhibition of cathepsin B through ligand substitutions.
It has been over 80 years since the antiarthritic properties of gold(I) complexes were first recognized. However, a detailed understanding of their mechanism of action has been slow to develop. One likely biological target of gold(I) is the cathepsin family of lysosomal cysteine proteases, enzymes involved in the inflammation and joint destruction that are hallmarks of rheumatoid arthritis (RA). We have previously shown that analogs of auranofin, a clinically available antiarthritic drug, inhibit cathepsin B. In this study, the extent to which the steric and electronic properties of the phosphine ligand can be modified to obtain enhanced potency against cathepsin B is investigated.
Gunatilleke
Shamila S
SS
Department of Chemistry, University of Southern California, Los Angeles, CA 90089, United States.
Barrios
Amy M
AM
D001310:Auranofin / Q000737:chemistry; D002384:Catalysis / Q000187:drug effects; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017612:Gold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D017612:Gold Compounds; D001310:Auranofin; D002401:Cathepsin B