Disease relevance of Monomercaptosuccinic acid

• Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity [1].
• In the presence of thiomalic acid, on the other hand, NaAuCl4 did not completely block tetanus tension even at 50 microM [2].
• MSF medium without mercaptosuccinic acid, but with rice starch, dextran or levan substituted for glucose and with Yersinia enterocolitica added, supported limited growth of the amoeba [3].
• Two women with rheumatoid arthritis developed erythema annulare centrifugum while receiving gold thiomalate therapy [4].
• A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis [5].

High impact information on Monomercaptosuccinic acid

• We propose that the inhibition of vascular cell adhesion molecule-1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate and not its gold component [6].
• Effect of gold sodium thiomalate and its thiomalate component on the in vitro expression of endothelial cell adhesion molecules [6].
• In contrast, concentrations of As(2)O(3) that alone are not capable of inducing apoptosis in NB4 cells induce apoptosis in the presence of the GPx inhibitor mercaptosuccinic acid [7].
• Upon weekly i.m. injections of disodium gold thiomalate (Na2AuTM) 100% of A.SW mice produced IgG autoantibodies to antinuclear Ag and nucleolar Ag, respectively; about 70% of C57BL/6 mice produced IgG antinuclear Ag, whereas DBA/2 mice were resistant [8].
• Three of the most potent inhibitors found in this study, mercaptosuccinate, penicillamine, and alpha-mercaptopropionylglycine, are currently used as slow-acting drugs in the treatment of rheumatoid arthritis [9].

Chemical compound and disease context of Monomercaptosuccinic acid

• The effect of gold sodium thiomalate and its constituent part, thiomalate, on the virus titres and the lysosomal enzyme activity in peritoneal macrophages of Swiss/A2G mice infected with the avirulent strain of Semliki Forest virus [10].
• To elucidate the natural course of gold and penicillamine nephropathy and to facilitate appropriate clinical management 54 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular gold thiomalate (21) or oral D penicillamine (33) were studied in detail throughout the whole of their renal illnesses [11].

Biological context of Monomercaptosuccinic acid

• To produce endogenous oxidative stress, 3-amino-1,2,4-triazole (ATZ) and mercaptosuccinic acid (MS), which are known to inhibit catalase and glutathione peroxidase activities, respectively, were used [12].
• Albumin did not protect against DNA damage induced by NADPH but was extremely effective at preventing DNA fragmentation arising from the suppression of glutathione peroxidase activity with mercaptosuccinate [13].
• Mercaptosuccinate, a specific inhibitor of the antioxidant enzyme glutathione peroxidase, also inhibited cell growth [14].
• Thiols containing hydroxyl groups [e.g., 2-mercaptoethanol (2-ME)] or amino groups [e.g., N-(2-mercaptopropionyl)glycine (MPG)], or that have flat structures on the AuNP surface, such as mercaptosuccinic acid, exhibit double-exponential kinetics with first rate constants of 0.51-2.83x10(-2) s(-1) and second rate constants of 6.0-23.4x10(-4) s(-1) [15].
• First, mercaptosuccinate was docked by Molecular and Quantum Mechanics at the active site in both isozymes, evidencing the role of different residues in the ligand-protein interaction [16].

Anatomical context of Monomercaptosuccinic acid

• The distribution of gold in Kupffer cells and in subcellular fractions of rat liver was studied at intervals following intraperitoneal injection of 195Au sodium thiomalate (Myochrysine) [17].
• The protective effect was completely inhibited with a GPx inhibitor, mercaptosuccinic acid, indicating that GPx released from thrombin/PAR-activated astrocytes is responsible for neuroprotection of hybrid neurons against thrombin cytotoxicity [18].
• The concentration of free thiomalate in the sonicates and cytosols of the HeMyo cells was decreased to 25-30% of the concentration found in the HE cells [19].
• Sodium thiomalate and sodium chloroaurate were also able to inhibit lymphocyte activation [20].
• Sodium aurothiomalate and thiomalic acid without gold both caused a dose-dependent growth inhibition of both cell lines when used in the concentration range 25-300 mumol/l culture medium and for four days' exposure [21].

Associations of Monomercaptosuccinic acid with other chemical compounds

• The voltage-induced assembly of mercaptosuccinic acid-stabilized Au nanoparticles of 1.5 +/- 0.4 nm diameter is investigated at the polarizable water/1,2-dichloroethane interface [22].
• Moreover, modulation of glutathione peroxidase activity by use of the specific inhibitor mercaptosuccinate (MS) or by the depletion of glutathione (using buthionine-S, R-sulfoximine, BSO), enhanced the UVA-dependent MMP-1 response [23].
• The stability of QDs capped with mercaptoacetic acid, MSA, and DHLA towards aggregation at low pH was found to correlate with the pK(a) of the ligands [24].
• We conclude that the cells can develop resistance to the antiproliferative effect of sodium aurothiomalate, and that the resistance may be due to their capacity to maintain low concentrations of free thiomalate in the sonicates and cytosols [19].
• This effect could be counteracted by the addition of catalase or mercaptosuccinate, indicating the role of hydrogen peroxide formed during ascorbate synthesis in the depletion of GSH [25].

Gene context of Monomercaptosuccinic acid

• Unlike that of SeGPx, the GPx activity of [Cys]GPx was only slightly inhibited by mercaptosuccinate [26].
• Inhibition of GPx by mercaptosuccinate led to an increase in the vulnerability of mature OLs to H2O2 as well as a reduction in catalase activity [27].
• Aminotriazole, an inhibitor of catalase, decreased the cytoprotective activity of PRS, whereas blocking of glutathione peroxidase by mercaptosuccinate had no effect [28].
• Genes known to be coordinatively regulated in response to growth arrest and DNA damage, GADD45 and GADD153, were induced compared to the housekeeping gene beta-ACTIN by equitoxic doses of hydrogen peroxide and mercaptosuccinate [14].
• The results indicated that at drug concentrations likely to be attained to vivo, phenylbutazone may significantly inhibit elastase, while gold thiomalate and mucopolysaccharide polysulfonic acid ester (MPSE; Arteparon) could limit the action of cathepsin G [29].

Analytical, diagnostic and therapeutic context of Monomercaptosuccinic acid

• Plasma concentrations and urinary excretion of free thiomalate were measured in 8 patients by high-performance liquid chromatography and electrochemical detection [30].
• Intramuscular injection of the purified drug to 2 healthy subjects produced easily detectable levels of thiomalate in both plasma and urine; 7.7 and 9.8% respectively of the doses given were recovered in urine as free thomalate within 4 h [31].
• Sodium thiosulfate, auranofin and sodium thiomalate gave positive patch test reactions [32].
• The complex formation of thiomalic acid (H3L) with Hg(II) and Pb(II) was investigated under physiological conditions of 37 degrees C and 0.15 mol dm-3 NaCl by potentiometric titrations using glass electrodes [33].
• It has been proposed that this activity may be used for nonimmune drug targeting to sites in the extra-cellular matrix such as the targeting of gold thiomalate to rheumatoid joints [34].

References