Anti-arthritis drugs
المؤلف:
Peter Atkins, Tina Overton, Jonathan Rourke, Mark Weller, and Fraser Armstrong
المصدر:
Shriver and Atkins Inorganic Chemistry ,5th E
الجزء والصفحة:
775
2025-10-28
64
Anti-arthritis drugs
Key point: Complexes of Au are effective against rheumatoid arthritis. Gold drugs are used in the treatment of rheumatoid arthritis, an inflammatory disease that affects the tissue around joints. The inflammation arises by the action of hydrolytic enzymes in cell compartments known as lysosomes that are associated with the Golgi apparatus (see Fig. 27.1). Although the mechanism of action is not established, it is known that Au accumulates in the lysosomes, and it is therefore possible that Au inhibits these O 64 N 65 Bleomycin hydrolytic enzymes. Another hypothesis is that Au(I) compounds deactivate singlet O2, a harmful species that can be formed by oxidation of superoxide. The mechanism for this reaction might involve promotion of intersystem crossing by the high spin-orbit coupling constant of the heavy element. Commonly administered drugs include sodium aurothiomalate (‘myochrisin’, 66), sodium aurothioglucose (‘solganol’, 67; the linkage between units is uncertain), and others, all of which feature Au(I) with linear coordination. Many are water-soluble polymers, but they cannot be administered orally because they undergo acid hydrolysis in the stomach. By contrast, the compound known as auranofin (68) can be given orally. Because Au(I) is chemically soft it is likely that it targets sulfur groups such as cysteine side chains in proteins. It is much more likely to survive in biological environments than Au (III), which is highly oxidizing. As expected, Au compounds lead to side effects, which include skin allergies as well as kidney and gastrointestinal problems.
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