Inhibition of Lysosomal Cysteine Proteases by a Series of Au(I) Complexes:  A Detailed Mechanistic Investigation

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 μM, depending on the substituents around the Au(I).