Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hydroxamic Acids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,207 records · Page 67Linked to original sources
PubMedDate not supplied

["Oxygen regulation" of the respiratory chain composition in the yeast Debaryomyces hansenii under multiple stress].

It was shown that two stress factors, hypoxia and hyperosmotic shock, if applied simultaneously to the yeast Debaryomyces hansenii, display an antagonistic mode of interaction, which results in an increased degree of halophily of this microorganism under microaerobic conditions. Studies of the effects of respiration inhibitors (sodium azide and salicyl hydroxamic acid, SHA) and of the pattern of changes in the composition of the respiratory chain of Debaryomyces hansenii under the stated stress conditions led to the suggestion of three (or four) chains of electron transfer functioning simultaneously in the cell: the classical respiratory chain involving cytochrome-c oxidase, an alternative respiratory chain involving a cyanide- and azide-resistant oxidase, and additional respiratory chains involving oxidases resistant to salt, azide and SHA. Thus, the antagonistic mode of interaction between hypoxia and hyperosmotic shock results from the redirection of the electron flow from the salt-susceptible respiratory systems to the salt-unsusceptible ones encoded by "the hypoxia genes" and activated (induced) under microaerobic conditions.

Anaerobiosis↗
PubMed2006

Histone deacetylase inhibitors as novel anti-inflammatory agents.

Histone acetylation regulates inflammatory gene expression and also plays a role in diverse functions such as DNA repair and cell proliferation. Changes in histone acetylation patterns have been reported in many human diseases, particularly cancer, and investigators have used histone deacetylase inhibitors (eg, suberoylanilide hydroxamic acid and MS-275) against many malignancies. In vitro and in vivo data in a number of cell types and animal models of disease indicate that selective histone deacetylase inhibitors may have the potential to act as anti-inflammatory agents possibly acting through non-histone proteins. More evidence is required concerning the long-term safety of these agents, for example, lung destruction, and in comparison with currently used therapies.

Animals↗
PubMed1991

Selective inhibition of glucuronidation by 2,2,2-triphenylethyl-UDP in isolated rat hepatocytes: conjugation of harmol, 3,3',5-triiodothyronine, and N-hydroxy-2-acetylaminofluorene.

2,2,2-Triphenylethyl-UDP (TPEU) was synthesized as an analogue of the transition state of the glucuronidation reaction catalyzed by UDP-glucuronosyltransferase; it contains both a uridine and an acceptor substrate moiety. It inhibits rat liver microsomal UDP-glucuronosyltransferase [Eur. J. Biochem. 188:309-312 (1990)]. In the present work, TPEU was tested as an inhibitor of glucuronidation in intact rat hepatocytes. Two phenols (harmol and 3,3',5-triiodothyronine) and a hydroxamic acid (N-hydroxy-2-acetylaminofluorene) were used as substrates for glucuronidation. The glucuronidation of these substrates was strongly decreased by TPEU at 0.3-5 mM. Up to 5 mM TPEU did not kill the cells, as shown by unimpaired trypan blue exclusion at the end of the incubation. When glucuronidation was inhibited, the sulfation of harmol increased, as did the production of reactive species generated from N-hydroxy-2-acetylaminofluorene that bind to cellular macromolecules. This indicates that a decreased substrate consumption by loss of glucuronidation leads to increased conversion by competing pathways. The results show, therefore, that TPEU is an effective inhibitor of glucuronidation in this cellular system in vitro.

Animals↗
PubMed1990

Metabolism and biodisposition of heterocyclic amines.

The metabolic pathways of activation and detoxification of heterocyclic aromatic amines are similar to those reported for other aromatic amines. In vitro studies have shown that oxidation of the exocyclic amine group by cytochrome P450 results in formation of the mutagenic N-hydroxylamine derivatives. However, metastable conjugates of the hydroxyamino metabolites have not been identified in biological fluids such as bile or urine of rodents. This is in contrast to the aromatic amines 2-acetylaminofluorene and 4-aminobiphenyl in which both the hydroxamic acid and the N-glucuronide of the hydroxylamine have been identified (Miller et al., 1960; Radomski et al., 1973). This suggests that either very low levels of the N-hydroxyamino metabolites of heterocyclic amines are formed or that they are not stable and react rapidly. Phase II conjugation reactions include N-glucuronidation and the unusual pathway of sulfamate formation for several of these amines including IQ and MeIQx. Conjugation to glutathione has not been reported to be a major route of in vivo metabolism and detoxification of heterocyclic amines. Studies conducted in vitro are few and inconclusive. One study has shown that glutathione may serve both to activate as well as to detoxify hydroxyamino-Trp-P-2 (Saito et al., 1983). While a second study demonstrated that depletion of cellular glutathione increased the binding of Trp-P-2 metabolites to DNA in hepatocytes (Mita et al., 1982). Thus the role that glutathione plays in protecting the cell against this class of genotoxins merits further investigation. Much data has been gathered on human exposure to heterocyclic amines and mechanisms of genotoxicity have been elucidated, however, risk estimation of cancer development in humans by these carcinogens is still uncertain. There may be differences between man and rodents in the absorption, metabolism and activation versus detoxification as well as rates of excretion of heterocyclic amines. Humans also are exposed to many other carcinogens and potential tumor promoters (Sugimura, and Sato, 1983). Tumor promoters may enhance the effects of carcinogens. Fortunately, there also are tumor inhibiting factors in the diet which may weaken the biological activity of carcinogens (Wattenberg, 1985). Such variables make it difficult to extrapolate carcinogenicity data from animal experiments to assess risk to human cancer development.(ABSTRACT TRUNCATED AT 400 WORDS)

Amines↗
PubMedDate not supplied

[Determination of the transferase activity of L-asparaginase].

A method for determination of the transferase activity of 1-asparaginase in presence of hydroxylamine is developed. The optimally determined quantity of the enzyme was from 0.7 to 20 i. u. The conditions optimal for the enzymatic reaction and for quantitative estimation of 1-aspartyl-beta-hydroxamic acid were studied. The transferase and hydrolase activities of 1-asparaginase from E. coli were compared. The enzyme catalyzed at equal rates hydrolysis and hydroxylaminolysis of 1-asparagine.

Asparaginase↗
PubMed1988

Induction of repair synthesis of DNA in mammary and urinary bladder epithelial cells by N-hydroxy derivatives of carcinogenic arylamines.

Unscheduled DNA synthesis (UDS)-inducing activity was used as a parameter to estimate the abilities of rat mammary epithelial cells and urothelial cells from various species to activate carcinogenic aromatic amine derivatives. The N-hydroxy, N-hydroxy-N-acetyl, N-hydroxy-N-glucuronosyl derivatives of 2-aminofluorene (2-AF) and 4-aminobiphenyl (4-ABP) induced UDS in primary cultures of rat mammary epithelial cells, but 2-AF, the O-glucuronide of N-hydroxy-N-acetyl-2-AF (N-OH-AAF) and 4-ABP did not. Neither the activity of N-OH-AAF, N-hydroxy-N-formyl-2-AF, nor N-acetoxy-N-acetyl-2-AF was significantly altered by paraoxon, an inhibitor of microsomal N-deacetylase. Although N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMABP) also induced UDS, its N-acetyl derivative, which can not be activated by intramolecular, N,O-acetyltransfer, did not. Similarly, rat urothelial cells were responsive to the UDS-inducing activity of this hydroxylamine, but not the hydroxamic acid. In contrast, dog urothelial cells were responsive to both compounds. The UDS-inducing activity of N-OH-AAF was inhibited by paraoxon in the dog, but not in rat urothelial cells. N-Hydroxy-N,N'-diacetylbenzidine induced UDS in the urothelial cells of dog, rat, and rabbit, and a human urothelial cell line, HCV-29, whereas benzidine, N-acetylbenzidine, and N,N'-diacetylbenzidine did not. Co-treatment with 12-O-tetradecanoylphorbol-13-acetate did not enable benzidine to induce UDS in dog urothelial cells. Rat mammary epithelial cells activated N-OH-DMABP by acetyl coenzyme A-dependent O-acetylation and N-OH-AAF by N,O-acetyltransfer. They could not N-deacetylate N-OH-AAF. These results suggest that rat mammary and bladder epithelial cells are capable of activating N-arylhydroxylamine metabolites of these carcinogens, probably by N,O-acetyltransfer and O-acetylation, whereas dog urothelial cells are more likely to activate these metabolites by N-deacetylation and a reaction that has yet to be identified.

Aminobiphenyl Compounds↗
PubMed1979

Mutants of Arthroderma benhamiae.

The object of these studies was to isolate conditionally lethal mutants of Arthroderma benhamiae whose vegetative growth was temperature sensitive (ts). Three sorts of mutants were derived from nitrosoguanidine treatment of the microconidia of A. benhamiae: (i) ts "pleomorphic", (ii) ts "non-pleomorphic", and (iii) slow growers (sg) which were not temperature sensitive. The growth of wild type A. benhamiae, as measured by colony diameters, was 6 mm/day at 37 degrees C (chosen as non-permissive for screening mutants) and 5 mm/day at 25 degrees C (chosen as permissive for screening mutants). Growth of mutants of the first sort was virtually stopped at 37 degrees C but their growth at 25 degrees C was more rapid than that of wild type. The colony texture of these mutants was downy and their mycelium sterile. They failed to mate with parents of opposite mating type. These mutants were considered to be ts "pleomorphic". The second sort of mutants were ts "non-pleomorphic". Two isolates of this kind were recovered. They grew normally at 25 degrees C but their growth at 37 degrees C was reduced 50--70% of that of wild type. The nature of the temperature sensitive defect has not been identified. The third sort of mutant occurred very frequently. These isolates were slow growers (sg) regardless of temperature of incubation and their response to the respiratory inhibitors antimycin and salicyl hydroxamic acid suggested a defect in mitochondrial ribosome assembly and deficiencies in cytochromes not unlike those observed in the poky mutants of Neurospora. Two of the sg-mutants (sg 2 and sg3) produced abundant cleistothecia with asci and ascospores when back crossed to parents of opposite mating type. The sg 5 mutant produced cleistothecia but no ascospores. The ergosterol content of the sg 2 mutant was nearly the same as that of wild type while the ergosterol content of sg 3 was somewhat reduced and that of sg 5 was markedly reduced as compared to that of wild type. Thus the ergosterol content seems to play some role in sexual reproduction of A. benhamiae. The pattern of sensitivity to amphotericin B also reflected differences in the sterol content of the mutants, i.e., the two mutants with some alteration in their ergosterol content, sg 3 and sg 5 were more resistant to the antibiotic. During the course of these studies a number of variants were observed that produced different sorts and degrees of pigmentation of the reverse of their colonies. One stable variant of this kind gave rise to colonies with a red reverse when incubated at 37 degrees C and a yellow reverse when incubated at 25 degrees C. When plates were shifted from one temperature to another the next wave of growth was the color specified by the temperature.

Ascomycota↗
PubMed1983

New dextran derivatives. I. Nitrogen containing derivatives.

Three new derivatives of dextran were obtained: 3-morpholine-2-hydroxypropyl ether of dextran (I), hydroxamic acid of carboxymethyl dextran (II), and oxime of ketodextran (III). All the three derivatives exhibited low toxicity at parenteral administration to laboratory animals. (I) and (II) showed the capability of weakening the activity of tetanus and malignant edema toxins. Additionally, (I) showed immunotropic activity. Biological activity was observed when the derivative (I) had been obtained from dextran of the molecular weight 4000. At the molecular weight 20,000 the activity did not appear. Similarly, no activity was observed under oral administration.

Animals↗
PubMed1984

Siderophores of bacteria and fungi.

Siderophore-mediated iron assimilation systems are widely distributed in bacteria and fungi. The systems are comprised of low molecular weight ferric-ion specific ligands (siderophores) and cognate cell-bound receptor and utilization components. Most siderophores are classed chemically as hydroxamic acids or catechols; expression of both types is regulated by iron. Of the various siderophore systems present in E. coli, the enterobactin and aerobactin genes, encoded on the chromosome and pColV respectively, have been the most intensively studied to date as regards their molecular genetics.

Bacteria↗
PubMed1984

Metabolic activation and genotoxicity of N-hydroxy-2-acetylaminofluorene and N-hydroxyphenacetin derivatives in Reuber (H4-II-E) hepatoma cells.

Derivatives of both N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxyphenacetin (N-OH-P) were tested for their ability to cause DNA damage in Reuber (H4-II-E) cells using the alkaline elution technique. Reuber cells are devoid of N-OH-AAF deacylase, N,O-acyltransferase, and sulfotransferase activities. The hydroxamic acids themselves caused very little DNA damage, while N-hydroxy-2-aminofluorine (20 to 100 microM), N-hydroxyphenetidine (20 to 200 microM), and p-nitrosophenetole (10 to 100 microM) all caused dose-dependent damage. The dose-dependent DNA damage caused by N-acetoxy-2-acetylaminofluorene (5 to 25 microM) was completely inhibited by the deacylase inhibitor paraoxon (100 microM). In the presence of both partially purified rabbit liver cytosolic N,O-acyltransferase and guinea pig liver microsomal deacylase, N-OH-AAF was genotoxic. Neither paraoxon nor tRNA had any effect on the DNA damage induced by N-OH-AAF in the presence of N,O-acyltransferase, while paraoxon completely inhibited the damage when N-OH-AAF was incubated in the presence of guinea pig deacylase, and N-OH-P only caused slight DNA damage at higher concentrations of enzyme. In addition, partially purified guinea pig liver deacylase and N-OH-AAF (25 microM) caused 2600 revertants in the Salmonella test system, while only 380 revertants were seen with a 40-fold greater concentration of N-OH-P (1000 microM). The mutagenicity of both N-OH-AAF and N-OH-P was completely inhibited by paraoxon. Thus, it is clear that metabolites of N-OH-AAF formed outside the cell are capable of passing both the cellular and nuclear membranes to cause genotoxicity. Metabolic activation of N-OH-AAF by either the membrane-bound deacylase or the cytosolic N,O-acyltransferase caused genotoxicity via a deacetylation process. Metabolic activation of N-OH-P by guinea pig deacylase caused low levels of DNA damage, whereas activation by N,O-acyltransferase was not sufficient to cause genotoxicity.

2-Acetylaminofluorene↗
PubMed1982

Cyanide-resistant respiration in a respiration-deficient mutant of Saccharomyces cerevisae.

A respiration-deficient mutant of Saccharomyces cerevisiae, grown aerobically with glucose as the sole source of energy and carbon, showed residual respiration resistant to cyanide. The differential sensitivity of cell fractions to inhibition by hydroxamic acids and carbon monoxide suggested that more than one type of organelle, probably mitochondria and microsomes, was involved in the consumption of oxygen.

Carbon Monoxide↗
PubMedDate not supplied

[Electron transport chains of Torulopsis candida].

The systems of electron transport to oxygen and other acceptors were analyzed during endogenous respiration of Torulopsis candida resting cells taken at the logarithmic phase of growth of the culture in a medium containing glucose and hexadecane. The following electron transport chains were shown to function in the cells growing both on glucose and hexadecane: (1) the main (phosphorylating) respiration chain inhibited by cyanide and antimycin A and comprising flavoproteins and cytochromes b, c and a+a3; (2) the cyanide resistant electron transport chain inhibited by hydroxamic acids (it seems to function more intensively in the cells grown on glucose); (3) the chain of electron transport to H2O2 which is blocked with antimycin A and includes flavoproteins, cytochromes b and c, and apparently cytochrome c peroxidase; (4) the chain(s) containing cytochrome P-450 and found in the microsomal fraction of yeast cells grown on hexadecane.

Candida↗
PubMed1981

The respiration pathways of wild-type and petite mutants of Kluyveromyces lactis.

The existence of two alternative respiration pathways in Kluyveromyces lactis has been confirmed. Both pathways may be demonstrated in petite mutants of this yeast, suggesting that the major components in these pathways have an extramitochondrial origin. The antimycin A insensitive/sodium azide insensitive pathway (pathway I) is abolished by glucose repression of this yeast, whereas the antimycin A insensitive/sodium azide sensitive pathway (pathway II) is unaffected by this treatment. In K. lactis wild-type cells, the antimycin A insensitive/sodium azide sensitive respiration pathway (pathway II) is inhibited by salicyl hydroxamic acid, and this inhibition may be overcome upon addition of exogenous Fe3+ ions. This pathway in petite cells is unaffected by the presence of this inhibitor. The possible reasons for this are discussed.

Antimycin A↗
PubMed1994

[The mechanisms of the changes in coronary vascular resistance in anaphylactic shock].

Anaphylactic shock decreased the coronary perfusion pressure, systemic arterial pressure and cardiac output in anesthetised dogs. After combined inhibition of cyclo-oxygenase and lipoxygenase with linoleate-hydroxamic acid, the anaphylactic coronary constriction and morphological cardiac lesions were considerably diminished. Activation of the lipoxygenase pathway seems to play a major role in development of the coronary constriction in anaphylaxis.

Anaphylaxis↗
PubMed1995

T cell gelatinases mediate basement membrane transmigration in vitro.

T cell homing into extravascular sites requires penetration across the subendothelial basal lamina, a specialized nonfibrillar connective tissue structure that anchors endothelial cells to parenchymal surfaces. Herein, we show that normal human T cells express gelatinases A and B, two matrix metalloproteinases active against the major basal lamina constituents, collagen types IV and V. Expression is confirmed at both the mRNA and protein levels. Gelatinase B is expressed constitutively, whereas gelatinases A and B expression is induced by T cell activation. In vitro migration of resting T cells across a basal lamina equivalent is mediated by gelatinase B, because it is specifically blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. Inhibition of T cell homing by interference with gelatinase function may represent a useful approach to the treatment of T cell-mediated autoimmune diseases.

Base Sequence↗
PubMed1994

Towards an understanding of the reactivity of E. coli R2 ribonucleotide reductase: a mechanistic approach to inactivation.

Five categories of reaction of the Escherichia coli R2 protein of ribonucleotide reductase (RNR) are defined from mechanistic studies with hydroxyurea, methylhydroxylamine, hydroxamic acid derivatives, long-lived organic radicals of which methyl viologen MV+ is a good example, hydrazine, catechol and their derivatives. Attention is focused on whether a particular reagent reduces only the tyrosyl radical (Tyr.) giving metR2, or the Tyr. and Fe(III)2 in consecutive steps to give fully reduced R2. In the case of hydrazine (N2H4), reduction of both the Tyr and Fe(III)2 occurs in a uniphasic process, while with di-imide (N2H2) it has already been demonstrated that the Tyr. is reduced and that Fe(II)Fe(III) semi-metR2 is formed. A further mechanism is observed with catechol and catechol-like derivatives (in this work Didox), in which there is reduction of the Tyr. in the first stage, followed by scavenging of the Fe(III) in the second. The latter offers a more permanent inactivation of R2, meriting more extensive study in the context of cancer drug therapy. Comparative studies on mouse R2 suggest that the Tyr. and Fe(III)2 of mammalian R2 forms may be more exposed, and as compared to E. coli R2 are approximately an order of magnitude more reactive.

Antineoplastic Agents↗