Dehydrogenases inhibitors

HMR 1726, Terifluno-mide Dihydro-orotate dehydrogenase inhibitor Reduced number of active lesions Multiple Sclerosis... 

Rationale for the Use of 17 -Hydroxysteroid-dehydrogenase Inhibitors in Cancer Treatment... 

Greene JG, Greenamyre JT (1995) Characterization of the excitotoxic potential of the reversible succinate dehydrogenase inhibitor malonate. J Neurochem 64 430-436 Gunne LM, Andren PE (1993) An animal model for coexisting tardive dyskinesia and tardive parkinsonism—a glutamate hypothesis for tardive dyskinesia. Clin Neuropharmacol 16 90-95... 

Mechanism of Action An alcohol dehydrogenase inhibitor that inhibits the enzyme that catalyzes the metabolism of ethanol, ethylene glycol, and methanol to their toxic metabolites. Therapeutic Effect Inhibits conversion of ethylene glycol and methanol into toxic metabolites. 

Drug Treatment of Chronic Alcoholism (Aldehyde Dehydrogenase Inhibitors)... 

Trilostane is 13-17 hydroxysteroid dehydrogenase inhibitor that interferes with the synthesis of adrenal and gonadal hormones and is comparable to aminoglutethimide. Trilostane s adverse effects are predominantly gastrointestinal adverse effects occur in about 50% of patients with both trilostane and aminoglutethimide. There is no cross-resistance or crossover of side effects between these compounds. Trilostane is not available in the USA. 

Andrews, R C., Rooyackers, O., Walker, B. R (2003) Effects of the llfi-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab 88, 285-291. 

Helander, A. Lindahl-Kiessling, K. (1991) Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor. Mutat. Res., 264, 103-107... 

Clearly, this method cannot be applied to systems in which there are irreversible chemical processes. It is most suitable for situations involving simple ligand binding (such as NAD+ with a dehydrogenase), inhibitor binding, or conformational changes in the protein. There have been some attempts to combine the temperature-jump with the stopped-flow method. 

Baslow M. H., Suckow R. F., and Hungund B. L. (2000). Effects of ethanol and of alcohol dehydrogenase inhibitors on the reduction of N-acetylaspartate levels of brain in mice in vivo a search for substances that may have therapeutic value in the treatment of Canavan disease. J. Inherit. Metab Dis. 23 684-692. 

Excitotoxic lesions generated in primates using NMDA receptor agonists such as quinolinic acid cause neuronal loss similar to that found in HD, emphasizing, the potential role of excitotoxicity in HD. Intrastriatal injections of the reversible succinate dehydrogenase inhibitor, malonate, into rats caused a decrease in ATP levels and increased lactate and excitotoxic lesions, which could be prevented by NMDA antagonists. 

Chen, J. L., Gerwick, W. H., Schatzman, R., and Laney, M., Isorawsonol and related IMP dehydrogenase inhibitors from the tropical green alga Avrainvillea rawsonii, J. Nat. Prod., 57, 947, 1994. 

Some bioactive flavones include aldose reductase inhibitors (apigenin 4 -methyl ether (acacetin), apigenin 7-0-apioside (apiin), 5,7-dihydroxyflavone (chrysin) and luteolin) antiinflammatory 5-LOX inhibitors (5,6,7-trihydroxyflavone (baicalein), 5,6,3, 4 -tetrahydroxy 7-methoxyflavone (pedalitin), 5,3, 4 -trihydroxy 6,7-dimethoxyflavone (cirsiliol, 6-0-methylpedalitin) and flavone) a COX inhibitor (flavone) iodothyronine deiodinase inhibitors (acacetin, chrysin and luteolin) a NADH and succinate dehydrogenase inhibitor (luteolin) millet-derived, goitrogenic inhibitors of thyroid peroxidase (flavone C-glycosides orientin and vitexin) and protein kinase inhibitors (acacetin, apigenin, baicalein, flavone, luteolin, 5,7,3, 4, 5 -pentahydroxyflavone (tricetin) and tricetin 3, 4, 5 -trimethyl ether). 

Some bioactive flavonols include aldose reductase inhibitors (axillarin (5,7,3, 4 -tetrahy-droxy-6-methoxyflavone), 2,3-dihydroquercetin (taxifolin), 6-hydroxykaempferol (galetin), hyperin (quercetin 3-0-galactoside), isoquercetrin, morin (3,5,7,2, 4 -pentahydroxy-flavone), quercetin, quercitrin and rutin) anti-inflammatory 5-LOX inhibitors (fisetin (3,7,3, 4 -tetrahydroxyflavone), kaempferol, morin, myricetin, quercetin and rutin) a GOX inhibitor (galangin (3,5,7-trihydroxyflavone)) iodothyronine deiodinase inhibitors (fisetin, kaempferol and morin) NADH and succinate dehydrogenase inhibitors (fisetin and myricetin) and protein kinase inhibitors (fisetin, galangin, isorhamnetin, kaempferide... 

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