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Chemical Compound Review

aldoximes     N-methylidenehydroxylamine

Synonyms: ketoxime, Formoxime, Nitrone, ketoximes, oximes, ...
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Disease relevance of oximes


Psychiatry related information on oximes

  • 1-aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one oximes as potent dopamine D4 receptor agonists for the treatment of erectile dysfunction [6].
  • The in vivo cytoprotective effects of alpha-phenyl-t-butyl nitrone against striatal excitotoxic lesions suggest that antioxidants could be used as potential neuroprotective agents in Huntington's disease, which has been suggested to involve excitotoxicity [7].
  • PBN (alpha-phenyl-tert-butyl nitrone), one of the more widely used nitrones for this purpose, has been shown to have potent pharmacologic activities in models of a number of aging-related diseases, most notably the neurodegenerative diseases of stroke and Alzheimer's disease [8].
  • The carboxamides Ie and IVe were obtained from the oximes Ic and IVc via the cyano derivatives Id and IVd [9].

High impact information on oximes

  • Complex V-deficient fibroblasts, which showed a high SOD induction and stained positive for all studied apoptosis markers, were successfully rescued by perfluoro-tris-phenyl nitrone, an antioxidant spin-trap molecule [10].
  • Male Wistar rats were fed a choline-deficient, L-amino acid-defined (CDAA) diet alone or in combination with a nitrone-based free radical trapping agent, phenyl N-tert-butyl nitrone (PBN) in the drinking water at the concentrations of 0.013, 0.065, and 0.130% for 12 weeks [11].
  • This nitrone (4) reacts with alpha-hydroxyethyl radical with a second order rate constant of 1.7 x 10(5) M-1 s-1 to give a characteristic ESR spectrum [12].
  • When LPO reacted with GSH in the presence of DMPO, we detected an LPO radical-derived DMPO nitrone adduct using enzyme-linked immunosorbent assay and Western blotting [13].
  • We investigated the anti-apoptotic effects of intracellular and extracellular nitric oxide (*NO) donors, iron chelators, cell-permeable superoxide dismutase (SOD), glutathione peroxidase mimetics, and nitrone spin traps [14].

Chemical compound and disease context of oximes


Biological context of oximes

  • N-t-butyl hydroxylamine, a hydrolysis product of alpha-phenyl-N-t-butyl nitrone, is more potent in delaying senescence in human lung fibroblasts [20].
  • Therefore, in our study, we selected 11 acyclic and cyclic nitrone spin traps with diverse properties to determine their pharmacokinetics in mice [21].
  • In a detailed analysis of the substrate specificities of the recombinant enzymes heterologously expressed in yeast (Saccharomyces cerevisiae), we show that aliphatic oximes derived from chain-elongated homologs of methionine are efficiently metabolized by CYP83A1, whereas CYP83B1 metabolizes these substrates with very low efficiency [22].
  • Further, they suggest that the improved performance of dimeric oximes is conferred by two-site binding with one oxime pointing toward the diisopropyl ester at the catalytic site of hAChE and the other anchored at the peripheral site [23].
  • The nitrone slowly decomposed in acidic aqueous solution at ambient temperature and also underwent in-source, thermal-induced hydrolysis during electrospray ionization mass spectrometric analysis [24].

Anatomical context of oximes

  • In addition, we were able to demonstrate the presence of hemoglobin radical-derived nitrone adducts inside red blood cells exposed to H2O2 and DMPO [25].
  • Studies of the transfer constant of [14C]NXY-059 showed that, in contrast to PBN, this more soluble nitrone penetrates the blood-brain barrier less extensively [15].
  • The results showed that myeloperoxidase-catalyzed redox cycling of phenol in HL-60 cells led to intracellular formation of glutathionyl radicals detected as GS-DMPO nitrone [26].
  • Indeed, in HOCl-treated hepatocytes, catalase and protein-DMPO nitrone adducts were colocalized in the cells' peroxisomes [27].
  • The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [3H]pirenzepine and [3H]-N-methylscopolamine as radioligands [28].

Associations of oximes with other chemical compounds

  • Furthermore, antiapoptotic antioxidants (e.g. FeTBAP, ebselen, and alpha-phenyl-tert-butyl nitrone) inhibited DOX-induced eNOS transcription [29].
  • Methyl radicals were identified by spin-trapping experiments with alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone and tert-nitrosobutane [30].
  • The nitrone complexes [(eta(5)-C(5)Me(5))M{(R)-Prophos}(nitrone)](SbF(6))(2) (M = Rh, nitrone = 1-pyrrolidine N-oxide (5), 2,3,4,5,-tetrahydropyridine N-oxide (6), 3,4-dihydroisoquinoline N-oxide (7); M = Ir, nitrone = 1-pyrrolidine N-oxide (8)) have been isolated and characterized including the X-ray crystal structure of compounds 6 and 8 [31].
  • We have previously reported that phenyl N-tert-butyl nitrone (PBN) inhibits the induction of inducible nitric oxide synthase (iNOS) and, thus, prevents the overproduction of nitric oxide (NO), resulting in the reduction of endotoxin-mediated death in mice [32].
  • 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) spin trapping in conjunction with antibodies specific for the DMPO nitrone epitope was used on hydrogen peroxide-treated sperm whale and horse heart myoglobins to determine the site of protein nitrone adduct formation [33].
  • O-Trityl oximes of 5- and 6-iodoaldehydes undergo radical cyclization to produce oximes when treated in refluxing tetrahydrofuran (THF) with Bu3SnH, 1,1'-azobis(cyclohexanecarbonitrile), i-Pr2NEt, and diphenyl diselenide (PhSeSePh) [34].

Gene context of oximes


Analytical, diagnostic and therapeutic context of oximes


  1. Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone. Bolli, R., Patel, B.S., Jeroudi, M.O., Lai, E.K., McCay, P.B. J. Clin. Invest. (1988) [Pubmed]
  2. Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration. Gendelman, M., Halligan, N., Komorowski, R., Logan, B., Murphy, W.J., Blazar, B.R., Pritchard, K.A., Drobyski, W.R. Blood (2005) [Pubmed]
  3. Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. Ginsberg, M.D., Becker, D.A., Busto, R., Belayev, A., Zhang, Y., Khoutorova, L., Ley, J.J., Zhao, W., Belayev, L. Ann. Neurol. (2003) [Pubmed]
  4. Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps. Thomas, C.E., Ohlweiler, D.F., Carr, A.A., Nieduzak, T.R., Hay, D.A., Adams, G., Vaz, R., Bernotas, R.C. J. Biol. Chem. (1996) [Pubmed]
  5. Phenyl-{alpha}-tert-Butyl Nitrone Reverses Mitochondrial Decay in Acute Chagas' Disease. Wen, J.J., Bhatia, V., Popov, V.L., Garg, N.J. Am. J. Pathol. (2006) [Pubmed]
  6. 1-aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one oximes as potent dopamine D4 receptor agonists for the treatment of erectile dysfunction. Kolasa, T., Matulenko, M.A., Hakeem, A.A., Patel, M.V., Mortell, K., Bhatia, P., Henry, R., Nakane, M., Hsieh, G.C., Terranova, M.A., Uchic, M.E., Miller, L.N., Chang, R., Donnelly-Roberts, D.L., Namovic, M.T., Hollingsworth, P.R., Martino, B., El Kouhen, O., Marsh, K.C., Wetter, J.M., Moreland, R.B., Brioni, J.D., Stewart, A.O. J. Med. Chem. (2006) [Pubmed]
  7. Antioxidant treatment protects striatal neurons against excitotoxic insults. Nakao, N., Grasbon-Frodl, E.M., Widner, H., Brundin, P. Neuroscience (1996) [Pubmed]
  8. Nitrones as neuroprotectants and antiaging drugs. Floyd, R.A., Hensley, K., Forster, M.J., Kelleher-Anderson, J.A., Wood, P.L. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  9. Synthesis of Schiff bases of benzofuran with potential biological activity. Rahman, A.H., Ismail, E.M. Arzneimittel-Forschung. (1976) [Pubmed]
  10. Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA. Geromel, V., Kadhom, N., Cebalos-Picot, I., Ouari, O., Polidori, A., Munnich, A., Rötig, A., Rustin, P. Hum. Mol. Genet. (2001) [Pubmed]
  11. Inhibition by phenyl N-tert-butyl nitrone of early phase carcinogenesis in the livers of rats fed a choline-deficient, L-amino acid-defined diet. Nakae, D., Kotake, Y., Kishida, H., Hensley, K.L., Denda, A., Kobayashi, Y., Kitayama, W., Tsujiuchi, T., Sang, H., Stewart, C.A., Tabatabaie, T., Floyd, R.A., Konishi, Y. Cancer Res. (1998) [Pubmed]
  12. The use of fluorophore-containing spin traps as potential probes to localize free radicals in cells with fluorescence imaging methods. Pou, S., Bhan, A., Bhadti, V.S., Wu, S.Y., Hosmane, R.S., Rosen, G.M. FASEB J. (1995) [Pubmed]
  13. Protein radical formation during lactoperoxidase-mediated oxidation of the suicide substrate glutathione: immunochemical detection of a lactoperoxidase radical-derived 5,5-dimethyl-1-pyrroline N-oxide nitrone adduct. Guo, Q., Detweiler, C.D., Mason, R.P. J. Biol. Chem. (2004) [Pubmed]
  14. Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide. Peroxyl radical scavenging as an antiapoptotic mechanism. Kotamraju, S., Hogg, N., Joseph, J., Keefer, L.K., Kalyanaraman, B. J. Biol. Chem. (2001) [Pubmed]
  15. Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat. Kuroda, S., Tsuchidate, R., Smith, M.L., Maples, K.R., Siesjö, B.K. J. Cereb. Blood Flow Metab. (1999) [Pubmed]
  16. Atypical effect of some spin trapping agents: reversible inhibition of acetylcholinesterase. Milatovic, D., Radic, Z., Zivin, M., Dettbarn, W.D. Free Radic. Biol. Med. (2000) [Pubmed]
  17. Necrosis of the substantia nigra, pars reticulate, in flurothyl-induced status epilepticus is ameliorated by the spin trap alpha phenyl-N-tert-butyl nitrone. He, Q.P., Smith, M.L., Li, P.A., Siesjö, B.K. Free Radic. Biol. Med. (1997) [Pubmed]
  18. Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH acting as a highly potent antioxidant agent. Poeggeler, B., Durand, G., Polidori, A., Pappolla, M.A., Vega-Naredo, I., Coto-Montes, A., Böker, J., Hardeland, R., Pucci, B. J. Neurochem. (2005) [Pubmed]
  19. Effect of traumatic brain injury and nitrone radical scavengers on relative changes in regional cerebral blood flow and glucose uptake in rats. Marklund, N., Sihver, S., Långström, B., Bergström, M., Hillered, L. J. Neurotrauma (2002) [Pubmed]
  20. N-t-butyl hydroxylamine, a hydrolysis product of alpha-phenyl-N-t-butyl nitrone, is more potent in delaying senescence in human lung fibroblasts. Atamna, H., Paler-Martínez, A., Ames, B.N. J. Biol. Chem. (2000) [Pubmed]
  21. High-performance liquid chromatography study of the pharmacokinetics of various spin traps for application to in vivo spin trapping. Liu, K.J., Kotake, Y., Lee, M., Miyake, M., Sugden, K., Yu, Z., Swartz, H.M. Free Radic. Biol. Med. (1999) [Pubmed]
  22. CYP83A1 and CYP83B1, two nonredundant cytochrome P450 enzymes metabolizing oximes in the biosynthesis of glucosinolates in Arabidopsis. Naur, P., Petersen, B.L., Mikkelsen, M.D., Bak, S., Rasmussen, H., Olsen, C.E., Halkier, B.A. Plant Physiol. (2003) [Pubmed]
  23. Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Pang, Y.P., Kollmeyer, T.M., Hong, F., Lee, J.C., Hammond, P.I., Haugabouk, S.P., Brimijoin, S. Chem. Biol. (2003) [Pubmed]
  24. The importance of chromatographic separation in LC/MS/MS quantitation of drugs in biological fluids: detection, characterization, and synthesis of a previously unknown low-level nitrone metabolite of a substance P antagonist. Wu, Y., Farrell, J.T., Lynn, K., Euler, D., Kwei, G., Hwang, T.L., Qin, X.Z. Anal. Chem. (2003) [Pubmed]
  25. Immunochemical detection of hemoglobin-derived radicals formed by reaction with hydrogen peroxide: involvement of a protein-tyrosyl radical. Ramirez, D.C., Chen, Y.R., Mason, R.P. Free Radic. Biol. Med. (2003) [Pubmed]
  26. Myeloperoxidase-catalyzed redox-cycling of phenol promotes lipid peroxidation and thiol oxidation in HL-60 cells. Goldman, R., Claycamp, G.H., Sweetland, M.A., Sedlov, A.V., Tyurin, V.A., Kisin, E.R., Tyurina, Y.Y., Ritov, V.B., Wenger, S.L., Grant, S.G., Kagan, V.E. Free Radic. Biol. Med. (1999) [Pubmed]
  27. Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes. Bonini, M.G., Siraki, A.G., Atanassov, B.S., Mason, R.P. Free Radic. Biol. Med. (2007) [Pubmed]
  28. Synthesis and pharmacological characterization of O-alkynyloximes of tropinone and N-methylpiperidinone as muscarinic agonists. Xu, R., Sim, M.K., Go, M.L. J. Med. Chem. (1998) [Pubmed]
  29. Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium. Kalivendi, S.V., Kotamraju, S., Zhao, H., Joseph, J., Kalyanaraman, B. J. Biol. Chem. (2001) [Pubmed]
  30. Formation of 8-methylguanine as a result of DNA alkylation by methyl radicals generated during horseradish peroxidase-catalyzed oxidation of methylhydrazine. Augusto, O., Cavalieri, E.L., Rogan, E.G., RamaKrishna, N.V., Kolar, C. J. Biol. Chem. (1990) [Pubmed]
  31. Enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein catalyzed by (eta5-C5Me5)M{(R)-prophos} containing complexes (M = Rh, Ir; (R)-prophos = 1,2-bis(diphenylphosphino)propane): on the origin of the enantioselectivity. Carmona, D., Lamata, M.P., Viguri, F., Rodríguez, R., Oro, L.A., Lahoz, F.J., Balana, A.I., Tejero, T., Merino, P. J. Am. Chem. Soc. (2005) [Pubmed]
  32. Optimal time and dosage of phenyl N-tert-butyl nitrone (PBN) for the inhibition of nitric oxide synthase induction in mice. Miyajima, T., Kotake, Y. Free Radic. Biol. Med. (1997) [Pubmed]
  33. Identification of the myoglobin tyrosyl radical by immuno-spin trapping and its dimerization. Detweiler, C.D., Lardinois, O.M., Deterding, L.J., de Montellano, P.R., Tomer, K.B., Mason, R.P. Free Radic. Biol. Med. (2005) [Pubmed]
  34. Carbocyclization by radical closure onto O-trityl oximes: dramatic effect of diphenyl diselenide. Clive, D.L., Pham, M.P., Subedi, R. J. Am. Chem. Soc. (2007) [Pubmed]
  35. Oxygen free radicals enhance the nitric oxide-induced covalent NAD(+)-linkage to neuronal glyceraldehyde-3-phosphate dehydrogenase. Marin, P., Maus, M., Bockaert, J., Glowinski, J., Prémont, J. Biochem. J. (1995) [Pubmed]
  36. N-oxygenation of primary amines and hydroxylamines and retroreduction of hydroxylamines by adult human liver microsomes and adult human flavin-containing monooxygenase 3. Lin, J., Berkman, C.E., Cashman, J.R. Chem. Res. Toxicol. (1996) [Pubmed]
  37. Anti-inflammatory and anti-allergic activities of hydroxylamine and related compounds. Kataoka, H., Horiyama, S., Yamaki, M., Oku, H., Ishiguro, K., Katagi, T., Takayama, M., Semma, M., Ito, Y. Biol. Pharm. Bull. (2002) [Pubmed]
  38. Free radical generation as induced by ochratoxin A and its analogs in bacteria (Bacillus brevis). Hoehler, D., Marquardt, R.R., McIntosh, A.R., Xiao, H. J. Biol. Chem. (1996) [Pubmed]
  39. Mechanism-based chemopreventive strategies against etoposide-induced acute myeloid leukemia: free radical/antioxidant approach. Kagan, V.E., Yalowich, J.C., Borisenko, G.G., Tyurina, Y.Y., Tyurin, V.A., Thampatty, P., Fabisiak, J.P. Mol. Pharmacol. (1999) [Pubmed]
  40. Distribution of spin-trapping compounds in rat blood and brain: in vivo microdialysis determination. Cheng, H.Y., Liu, T., Feuerstein, G., Barone, F.C. Free Radic. Biol. Med. (1993) [Pubmed]
  41. Using anti-5,5-dimethyl-1-pyrroline N-oxide (anti-DMPO) to detect protein radicals in time and space with immuno-spin trapping. Mason, R.P. Free Radic. Biol. Med. (2004) [Pubmed]
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