Disease relevance of NSC 193440

• At one of these loci, most, but not all, mutations lead pleiotropically to cycloheximide hypersensitivity, and most of these, but not all, also confer pleiotropic hypersensitivity to salicylhydroxamic acid [1].
• Pleomorphism and the problem of recrudescent parasitaemia following treatment with salicylhydroxamic acid (SHAM) in African trypanosomiasis [2].
• The concomitant administration of salicylhydroxamic acid and glycerol to rats infected with T. brucei brucei results in a rapid clearance of parasitemia [3].
• We have used salicylhydroxamic acid (SHAM) to inhibit intraphagosomal myeloperoxidase activity in order to evaluate the role of this enzyme in the killing of Staphylococcus aureus by human neutrophils [4].
• Salicylhydroxamic acid (SHAM) inhibits O(2) photoreduction which protects nitrogenase activity in the cyanobacterium Synechococcus sp. RF-1 [5].

High impact information on NSC 193440

• Trypanosoma brucei possesses a non-cytochrome, salicylhydroxamic acid (SHAM)-sensitive ubiquinol:oxygen oxidoreductase known as trypanosome alternative oxidase (TAO) [6].
• While oxygen consumption was cyanide insensitive, inhibition occurred following treatment with complex III inhibitors and the alternative oxidase inhibitor, salicylhydroxamic acid (SHAM) [7].
• No differences in peroxidatic activity or inhibition by salicylhydroxamic acid were observed among any of the MPO isoforms or resolved protomers, but the latter were considerably more heat labile than dimeric forms of the enzyme and a monomeric form isolated from HL-60 cells [8].
• Coupling of the PSMA-specific monoclonal antibody, J591, to the vector was facilitated via the high-affinity interaction between phenyl(di)boronic acid and salicylhydroxamic acid molecules [9].
• The decrease in stable-isotope-labeled avenanthramides was suppressed by catalase, salicylhydroxamic acid, and sodium ascorbate, suggesting the involvement of peroxidase in the metabolism [10].

Biological context of NSC 193440

• 4. Another inhibitor of alternative electron transport, salicylhydroxamic acid, shows a complex mode of action; low concentrations (less than 0.5 mM) stimulate respiration and H2O2 production, whereas 2 mM-salicylhydroxamic acid inhibited respiration by 35% and stopped H2O2 production completely [11].
• Drug interaction studies with atovaquone and salicylhydroxamic acid indicate atovaquone's activity against P. falciparum in vitro is potentiated by this alternative oxidase inhibitor, with a sum fractional inhibitory concentration of 0 [12].
• Binding of salicylhydroxamic acid and several aromatic donor molecules to Arthromyces ramosus peroxidase, investigated by X-ray crystallography, optical difference spectroscopy, NMR relaxation, molecular dynamics, and kinetics [13].
• Salicylhydroxamic acid does not inhibit binding of 125I-labelled C3 to tonsil lymphocytes at concentrations that completely inhibit binding of 125I-labelled C3 to EAC142 cells via the nascent binding site of C3b [14].
• These three mutants, unlike the rho(-) and rho degrees "petite" mutants of Saccharomyces cerevisiae, can still grow on non-fermentable substrates, due to the development of a salicylhydroxamic acid (SHAM)-sensitive alternative pathway linked to phosphorylation at site 1 [15].

Anatomical context of NSC 193440

• Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) [16].
• These mitochondria have a high level of respiration that is not inhibited by cyanide but is inhibited by salicylhydroxamic acid [17].
• Salicylhydroxamic acid reductase, which catalyzes the reduction of salicylhydroxamic acid to salicylamide, was purified from rat liver cytosol [18].
• Salicylhydroxamic acid functionalized affinity membranes for specific immobilization of proteins and oligonucleotides [19].
• The rate of oxygen consumption in the erythrocytes is shown to be modulated by various agents: the respiratory inhibitors NaN3 and KCN (1 mM) reduced oxygen consumption 2-3-fold; salicylhydroxamic acid (2.5 mM) caused a 20% reduction in rate and 10 mM NaN3, completely blocked deoxygenation [20].

Associations of NSC 193440 with other chemical compounds

• A combination of salicylhydroxamic acid (SHAM) + cyanide (CN) is known to stimulate dark germination of Lactuca sativa L. seeds [21].
• At all atovaquone concentrations tested, the addition of the alternative oxidase inhibitor, salicylhydroxamic acid, resulted in a further decrease in the rate of parasite oxygen consumption [12].
• Energy production in bloodstream forms of African trypanosomes of the genus Trypanosoma involves two pathways unique to the parasite and which can be blocked by a combination of salicylhydroxamic acid (SHAM) and glycerol [22].
• The respiration of mitochondria grown in the presence of antimycin A was not inhibited by cyanide or antimycin A but was inhibited by salicylhydroxamic acid [23].
• In this study, we found that inhibition of TAO by the specific inhibitor salicylhydroxamic acid stimulates the formation of reactive oxygen species (ROS) in trypanosome mitochondria, resulting in mitochondrial alteration and increased oxidation of cellular proteins [24].

Gene context of NSC 193440

• Mitochondrial alternative oxidase (AOX) is the terminal oxidase responsible for cyanide-insensitive and salicylhydroxamic acid-sensitive respiration [25].
• Hence, salicylhydroxamic acid provides a versatile backbone for the generation of a family of acylating inhibitors of cyclooxygenase [26].
• Inhibition of the AOX (with salicylhydroxamic acid) decreases respiration rates less than the activity present before inhibition (i.e. measured with the 18O-fractionation technique) [27].
• The activation of 9 and 13-LOX, using different timing, leads to the formation of LOOH with a subsequent generation of jasmonates and IAA as highlighted by the addition on the potato tuber slices of salicylhydroxamic acid (SHAM), an inhibitor of LOX activity [28].
• Furthermore, a significant reduction of salicylhydroxamic acid and nicotinohydroxamic acid was also observed, when an electron donor of aldehyde oxidase was added, with liver cytosols from hamsters, guinea pigs, rats, and mice [29].

Analytical, diagnostic and therapeutic context of NSC 193440

• Determination of salicylhydroxamic acid, a trypanocidal agent, by reversed phase high-performance liquid chromatography [30].
• Prolinx, Inc. has developed a novel chemical affinity system that can be used for specific immobilization of proteins and other macromolecules via interaction of two small synthetic molecules, phenyldiboronic acid (PDBA) and salicylhydroxamic acid (SHA) [19].
• The protolysis equilibria of 2-hydroxybenzohydroxamic acid, H2SAX, have been studied at 25 degrees C in different ionic media by potentiometric titration with a glass electrode [31].

References