Aurothiomalate

Gold compounds were first used in 1929 by French doctors to treat rheumatoid arthritis. Two of the most commonly used are aurothiomalate (myocrisin) and aurothioglucose (solganol) (Figure 4.52), given by injection of their solutions in doses of up to 25 mg a week for some years. 

C4H5O4S 70-49-5) see Erythromycin monopropionate mercaptosuccinate Sodium aurothiomalate thionyl bromide... 

Rudge, S.R., Perrett, D., Swannell, A.J. and Drury, P.L. (1984) Circulating thiomalate after administration of disodium aurothiomalate impurity or active metabolite The Journal of Rheumatology, 11, 150-152. 

Danpure, C.J. and Lawson, K.J. (1977) Interaction of aurothiomalate and cystine. Biochemical Society Transactions, 5, 1366-1368. 

Larabee, J.L., Hocker, J.R. and Hanas, J.S. (2005) Mechanisms of aurothiomalate-Cys2His2 Zinc finger interactions. Chemical Research in Toxicology, 18, 1943-1954. 

Beverly, B. and Couri, D. (1987) Role of Myeloperoxidase (MPO) in Aurothiomalate Metabolism. Federation Proceedings, 46, 854. 

Hurst, N.P., Bell, A.L. and Nuki, G. (1986). Studies on the effect of D-pencillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis evidence for in vivo stimulation of monocytes. Ann. Rheum. Dis. 45, 37-43. 

Treatment of RA patients with various drugs was shown to affect free radical production by phagocytic cells. It was found that the therapy with gold compounds [252] and piroxicam [237] diminished superoxide production in RA patients. Surprisingly, Hurst et al. [253] reported that successful therapy with penicillamine or sodium aurothiomalate is accompanied by an increase in superoxide production and serum thiol levels. The mechanism of this phenomenon is unknown. Mur et al. [254] demonstrated that antirheumatic medication of RA patients caused reducing cytokine priming of superoxide generation. 

Fig. 18. X-ray crystal structure of the injectable antiarthritic complex gold(I)-aurothiomalate 88 (side-chain on S omitted) showing the double helical chains. The right-handed helix shown contains thiomalate ligands with the R absolute configuration. Au-S bond lengths 2.283 and 2.286 A S-Au-S angles 178.88° and 169.41°. Adapted from (419).

The first-line agents in the treatment of rheumatoid arthritis are non-steroidal anti-inflammatory drugs such as diclofenac. Diclofenac and indometacin, another NSAID, tend to have similar activity hov/ever, indometacin has a higher incidence of side-effects and therefore diclofenac is more appropriate for initial treatment. Sodium aurothiomalate is classified as a disease-modifying antirheumatic drug and is used as a second-line treatment in rheumatoid arthritis, but has been superseded by methotrexate, administered v/eekly. Paracetamol is often indicated in the management of osteoarthritis. Local intra-articular injections of dexamethasone may be administered for the relief of soft-tissue inflammatory conditions. 

Synonyms sodium aurothiomalate mercaptobutanedioic acid monogold (1+) sodium salt Myochrysine Mycocrisin Shiosol... 

Augite, Mossbauer spectrum of, 6 474 Au(PRj) fragment, addition to homonuclear gold cluster compounds, 39 329-332 Auranofin, 36 21 cytotoxicity, 36 22, 34 Auro-bis(thiosulfate), 36 18-19 Aurosomes, gold in, 36 21-22 Aurothioglucose, 36 18-19 Aurothiomalate, 36 18-21... 

Dimensional structures of small molecules that exhibit IL-1 modulating activities. They are tenidap, ciprofloxacin, 3-Deazaadenosine, (SK F 86002), E5110, DMARDs (Chloroquine, Auranofin, Sodium aurothiomalate and Dexamethasone) tiaprofenic acid, dexamethasone, tricyclic-ylidene-acetic acid and its derivative, Probucol, eicosapentenoic acid + docosahexenoic, pentoxifylline, Denbufylline, and Romazarit (Ro-31-3948). 

Antinflammatory DMARDs such as chloroquine, auranofin, sodium aurothiomalate, and dexamethasone have been shown to inhibit IL-1 synthesis [89]. Analogs of these compounds have exhibited potent inhibition of IL-1 a- induced cartilage resorption [90]. Elevated collagenase and proteoglycanase levels caused by IL-1 in human cartilage were found to be reduced by tiapro-... 

Gold compounds were first proved to be effective in a large double-blind trial in 1960. Because of their toxicity, they are used infrequently today. Their intramuscular formulations (aurothiomalate and aurothioglucose) contain 50% elemental gold. The oral formulation (auranofin) contains 29% elemental gold. 

This technique is a histochemical procedure to evaluate die hyahuonidase activity of spermatozoa. Using this technique, Waibel el al. evaluated the inhibition of mouse testicular hyaluronidase by sodium aurothiomalate [147]. Hirayama et al. 

Those that have been identified in recent times include flavonoids,212-214 aurothiomalate,215 hydrangenol,216 occurring in the leaves of Hydrangea, tannins,217 derivatives of tranilast,218 curcumin,219 an extract of the spice turmeric, glycyrrhizin,220 found in the roots and rhizomes of licorice (Glycyrrhiza glabra), used as an effective antiinflamatory agent in Chinese medicine. 

---