PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Nitro Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 469 records · Page 26Linked to original sources
PubMed1999

Enzymatic and nonenzymatic production of free radicals from the carcinogens 4-nitroquinoline N-oxide and 4-hydroxylaminoquinoline N-oxide.

The anion radicals of 4-nitroquinoline N-oxide (4-NQO) and 4-nitrosoquinoline N-oxide (4-NOQO) carcinogens were detected and characterized by electron spin resonance (ESR) spectroscopy. The structures of the radical intermediates were examined by density functional theory (DFT) at the level of hybrid unrestricted uBecke3LYP. The formation of superoxide anion radical catalyzed by flavin-containing enzymes such as cytochrome P450 reductase or xanthine oxidase in the presence of 4-NQO or 4-nitroquinoline N-oxide was studied by spin-trapping experiments. In this case, the ESR signal of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-superoxide radical adduct was observed, and its formation was inhibited by superoxide dismutase (SOD). No ESR signal was detected when the two-electron-transferring flavoenzyme DT-diaphorase (NADPH-quinone oxidoreductase) was used. The above is consistent with a one-electron reduction in the metabolism of these nitro compounds to anion free radicals by various flavoenzyme reductases.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1977

Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro.

There is now evidence that several classes of nitro compounds which have been used as radiosensitizers also function as cytotoxic agents specific for hypoxic cells. The 2-nitroimidazole, Ro-07-0582, (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) is a compound of this type, and its effectiveness as a cytotoxic agent is dependent on drug concentration, contact time and temperature. In vitro, Ro-07-0582 in air at 37 degrees C does not cause loss of cell viability at concentrations up to 2 mM, even when in contact for several days. In contrast, hypoxic cells do not tolerate much lower concentrations of drugs, even if the contact time is only a few hours. When the temperature is raised above 37 degrees C, there is a pronounced increase in the slope of the survival curves; for example, at 41 degrees C (for 1 mM Ro-07-0582, (200 microng/ml), the slope changes by a factor of 2-0 relative to that for 37 degrees C. For cells in air at 41 degrees C, as at 37 degrees C, there is no toxic effect at the concentration of drug tested. In the absence of drug, there is no cytotoxic effect of hyperthermia alone under these conditions. These results are discussed in terms of Arrhenius parameters.

Anaerobiosis↗
PubMed1982

Structure/activity relationships for the enhancement by electron-affinic drugs of the anti-tumour effect of CCNU.

Using a regrowth-delay assay, we investigated structure/activity relationships for the enhancement by electron-affinic agents of the anti-tumour effect of the nitrosourea CCNU against the KHT sarcoma in C3H mice. A series of neutral 2-nitroimidazoles similar in electron affinity but varying in octanol/water partition coefficient (PC) over 4 orders of magnitude (0.016- greater than 200, Misonidazole = 0.43) were examined at a fixed dose of 2.5 mmol/kg. A parabolic (quadratic) dependence of activity on log PC was observed. Analogues more hydrophilic than misonidazole (MISO) were inactive as were those with very high PCs (greater than 20). Those with PC 0.43--20 were usually more active than MISO, some considerably so. The fairly lipophilic 5-nitroimidazoles nimorazole and metronidazole (METRO) had similar activity to MISO, despite their reduced electron affinity. Two basic 2-nitroimidazoles more efficient as radiosensitizers in vitro likewise showed activity comparable to MISO. We also investigated several agents more electron-affinic than MISO, including some non-nitro compounds. Most were inactive at maximum tolerated doses, but nitrofurazone showed reasonable activity. Sensitizer dose-response curves were obtained for MISO, METRO and two of the most effective agents, benznidazole (Ro 07-1051) and Ro 07-1902. The two latter agents were both considerably more active than MISO at low doses (0.1--0.9 mmol/kg). These studies indicate that the structural features of electron-affinic agents responsible for the enhancement of KHT tumour response to CCNU, are quite different from those affecting radiosensitization, lipophilicity being particularly important. The microsomal enzyme-inhibitor SKF 525A increased the anti-tumour effect of CCNU, suggesting inhibition of CCNU metabolism as one possible mechanism contributing to chemosensitization by lipophilic electron-affinic agents in mice.

Animals↗
PubMed1995

Investigation of decomposition products of microwave digestion of food samples.

The involatile residues remaining after closed-vessel microwave digestion of various food samples, using nitric acid, with and without post-digestion treatment with hydrogen peroxide, have been studied. Decomposition products were found to include aliphatic and aromatic acids, nitro-compounds, oxalates and inorganic nitrates and phosphates. Measures of digestion completeness were provided by appearance, carbon content, infrared spectra and thin layer chromatograms of the residues, enabling a comparison of different digestion methods and sample types. Residual carbon levels varied linearly with the relative amounts of carboxylic acid and inorganic nitrate, as measured by infrared spectrometry of the residues. The formation of calcium oxalate was also a function of the degree of decomposition: the carboxylic acid: oxalate ratio increased in a logarithmic fashion with increasing residual carbon content. Particularly high levels of residual carbon from nitric acid digestion of milk powder, due largely to carboxylic acid residues, were substantially decreased by post-digestion treatment with hydrogen peroxide. However, nitrobenzoic acids, which proved major interferents in electrochemical analysis, were only removed by treatment with perchloric acid.

Food↗
PubMed2005

Protonated nitro group: structure, energy and conjugation.

Structure of protonated nitro compounds was investigated by calculations at the levels MP2(FC)/6-311++G(2d,2p)//MP2(FC)/6-311++G(2d,2p)(nitromethane and reference compounds) or B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p)(nitrobenzene and its 18 meta- and para-substituted derivatives). The group NO2H+ reveals many similarities with the isoelectronic group CO2H as the preferred conformation, conformational equilibrium, and stabilization by interaction (resonance) within the group quantified by means of isodesmic reactions. However, there is a difference in the interaction with donor groups (for instance in 4-nitroaniline) that is much stronger with NO2H+ than with CO2H. This interaction may be called resonance and may be described by standard resonance formulas, but these formulas predict only partially the geometry and cannot explain the great interaction energy.

Journal Article↗
PubMed2005

Potential analytical applications of differential fluorescence quenching: pyrene monomer and excimer emissions as sensors for electron deficient molecules.

Quenching of the monomer and excimer emissions from pyrene allows excellent discrimination in the detection of electron-deficient molecules; this characteristic could be used to detect explosives and for rapid screening of complex samples suspected of containing explosives. The method responds to electron deficient molecules other than nitro compounds (e.g., 1,4-dicyanobenzene), giving some false positives; in this case, however, the method is unlikely to lead to false negatives, a desirable characteristic in security-related applications.

Journal Article↗
PubMed1980

A new approach to time-resolved studies of ATP-requiring biological systems; laser flash photolysis of caged ATP.

2-Nitrobenzyl derivatives have been used for several years as photolabile protecting groups in synthetic organic chemistry. Recently, P3-1-(2-nitro phenylethyladenosine 5'-triphosphate "caged ATP" was synthesized and its photolysis was shown to generate ATP in situ. This and related reactions have great potential for structural and kinetic studies of both intact and soluble biological systems and it is thus important to define the kinetic characteristics of the photolytic reaction. Caged ATP (2.5 mM) was photolyzed at 347 nm by a single 30-nsec pulse from a frequency-doubled ruby laser of 25 mJ energy to generate 500 microM ATP. The kinetics of the overall reaction were determined by monitoring the kinetics of ATP-induced dissociation of actomyosin, a reaction of known kinetic characteristics. Release of 500 microM ATP was found to be controlled by a process having a rate constant of 2.2 X 10(9) [H+] sec-1 at 22 degrees C at pH 5.8-9.5, which corresponds to 220 sec-1 at pH 7. This process is believed to be the breakdown of an aci-nitro compound, which was identified on the basis of its spectral properties and the photochromicity of related 2-nitrobenzyl compounds.

Actomyosin↗
PubMed1996

Structure-activity relationships derived by machine learning: the use of atoms and their bond connectivities to predict mutagenicity by inductive logic programming.

We present a general approach to forming structure-activity relationships (SARs). This approach is based on representing chemical structure by atoms and their bond connectivities in combination with the inductive logic programming (ILP) algorithm PROGOL. Existing SAR methods describe chemical structure by using attributes which are general properties of an object. It is not possible to map chemical structure directly to attribute-based descriptions, as such descriptions have no internal organization. A more natural and general way to describe chemical structure is to use a relational description, where the internal construction of the description maps that of the object described. Our atom and bond connectivities representation is a relational description. ILP algorithms can form SARs with relational descriptions. We have tested the relational approach by investigating the SARs of 230 aromatic and heteroaromatic nitro compounds. These compounds had been split previously into two subsets, 188 compounds that were amenable to regression and 42 that were not. For the 188 compounds, a SAR was found that was as accurate as the best statistical or neural network-generated SARs. The PROGOL SAR has the advantages that it did not need the use of any indicator variables handcrafted by an expert, and the generated rules were easily comprehensible. For the 42 compounds, PROGOL formed a SAR that was significantly (P < 0.025) more accurate than linear regression, quadratic regression, and back-propagation. This SAR is based on an automatically generated structural alert for mutagenicity.

Algorithms↗
PubMed2005

Reconstitution and characterization of aminopyrrolnitrin oxygenase, a Rieske N-oxygenase that catalyzes unusual arylamine oxidation.

Rieske oxygenases catalyze a wide variety of important oxidation reactions. Here we report the characterization of a novel Rieske N-oxygenase, aminopyrrolnitrin oxygenase (PrnD) that catalyzes the unusual oxidation of an arylamine to an arylnitro group. PrnD from Pseudomonas fluorescens Pf5 was functionally expressed in Escherichia coli, and the activity of the purified PrnD was reconstituted, which required in vitro assembly of the Rieske iron-sulfur cluster into the protein and the presence of NADPH, FMN, and an E. coli flavin reductase SsuE. Biochemical and bioinformatics studies indicated that the reconstituted PrnD contains a Rieske iron-sulfur cluster and a mononuclear iron center that are formed by residues Cys(69), Cys(88), His(71), His(91), Asp(323), His(186), and His(191), respectively. The enzyme showed a limited range of substrate specificity and catalyzed the conversion of aminopyrrolnitrin into pyrrolnitrin with K(m) = 191 microM and k(cat) = 6.8 min(-1). Isotope labeling experiments with (18)O(2) and H(2)(18)O suggested that the oxygen atoms in the pyrrolnitrin product are derived exclusively from molecular oxygen. In addition, it was found that the oxygenation of the arylamine substrates catalyzed by PrnD occurs at the enzyme active site and does not involve free radical chain reactions. By analogy to known examples of arylamine oxidation, a catalytic mechanism for the bioconversion of amino pyrrolnitrin into pyrrolnitrin was proposed. Our results should facilitate further mechanistic and crystallographic studies of this arylamine oxygenase and may provide a new enzymatic route for the synthesis of aromatic nitro compounds from their corresponding aromatic amines.

Amines↗
PubMed1985

Non-nitro radiation sensitizers.

A review of the literature on radiosensitization reveals that at least some of the non-nitro compounds, such as metabolic inhibitors and membrane-active drugs, could be considered as potentially valuable radiosensitizers for possible use in future cancer radiotherapy.

Animals↗
PubMed1985

The influence of thiols on the pre-irradiation incubation effect of nitroimidazoles in E. coli cells.

The increase in the degree of radiosensitization of Escherichia coli cells following prolonged pre-irradiation incubation with nitroimidazoles is not correlated with the loss of intracellular non-protein thiols (NPSH) alone. The rates of reduction of the nitro compounds and the NPSH removal do not show strong dependencies on the lipophilicities of the nitroimidazoles whereas the highly lipophilic compound RGW-609 effects an increase in radiosensitization in a much shorter incubation time than the other nitroimidazoles. Exogenous dithiothreitol (DTT) increased the rate of reduction of misonidazole in the cells but did not alter the fraction converted to the amine. Added DTT (0.15 mmol dm-3) completely protected against the pre-irradiation incubation effect of misonidazole (2.5 mmol dm-3) when added at the start of the incubation but only partially protected when added before irradiation. It is suggested that NPSH can intercept metabolite(s) (or their precursors) of nitroimidazoles which can potentiate cell killing by radiation.

Biological Transport↗
PubMed1985

Electrolytic reduction of nitroheterocyclic drugs leads to biologically important damage in DNA.

The effect of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single-stranded phi X174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA.

Bacteriophage phi X 174↗
PubMed1986

Enhancement of misonidazole cytotoxicity by iron.

The toxicity of misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells in serum-free medium is enhanced by Fe(III)-EDTA. Enhancement of MISO cytotoxicity by a factor of 1.6 was seen with 2 microM Fe(III)-EDTA, while 200 microM Fe(III)-EDTA results in sensitization by a factor of 2.0. Treatment of CHO cells with the iron chelator desferal resulted in protection against the hypoxic cytotoxicity in MISO (approximate protection factor of 2.5 with 100 microM desferal). Similar results were obtained with Chinese hamster V79 cells. Fe(III)-EDTA also enhanced binding of [2-14C] MISO to cellular macromolecules while desferal decreased binding of MISO to cellular macromolecules. These results suggest that iron plays an important role in the reductive metabolism of MISO and that modification of the intracellular metal ion status may be a useful approach to modulating the biological effect of nitro compounds.

Animals↗
PubMed1992

A structured approach to occupational hygiene in the design and operation of fine chemical plant.

In order to ensure appropriate occupational hygiene controls can be incorporated in the design and operation of fine chemical plant, a structured scheme has been developed based upon the intrinsic hazard of the materials in use. The scheme provides guidelines for managing the inherent risks to health presented by the operation of such plant, including basic recommendations on the selection and operation of selected plant equipment. Although the scheme has focused on a carcinogenic ranking system for aromatic amines and nitro compounds, with suitable modifications its underlying philosophy and principles should be capable of application to any toxicological scheme for ranking the relative hazard of chemical substances.

Carcinogens↗
PubMed2005

Site-specific incorporation of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) into oligonucleotides using modified 'ultra-mild' DNA synthesis.

Aromatic amino and nitro compounds are potent carcinogens found in the environment that exert their toxic effects by reacting with DNA following metabolic activation. One important adduct is N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF), which has been extensively used in studies of the mechanisms of DNA repair and mutagenesis. Despite the importance of dG-AAF adducts in DNA, an efficient method for its incorporation into DNA using solid-phase synthesis is still missing. We report the development of a modified 'ultra-mild' DNA synthesis protocol that allows the incorporation of dG-AAF into oligonucleotides of any length accessible by solid-phase DNA synthesis with high efficiency and independent of sequence context. Key to this endeavor was the development of improved deprotection conditions (10% diisopropylamine in methanol supplemented with 0.25 M of beta-mercaptoethanol) designed to remove protecting groups of commercially available 'ultra-mild' phosphoramidite building blocks without compromising the integrity of the exquisitely base-labile acetyl group at N8 of dG-AAF. We demonstrate the suitability of these oligonucleotides in the nucleotide excision repair reaction. Our synthetic approach should facilitate comprehensive studies of the mechanisms of repair and mutagenesis induced by dG-AAF adducts in DNA and should be of general use for the incorporation of base-labile functionalities into DNA.

2-Acetylaminofluorene↗
PubMed1990

Parental occupation and intracranial neoplasms of childhood: results of a case-control interview study.

In 1983-1984, the authors conducted a case-control study of environmental factors and childhood brain tumor risk. Cases (n = 110) were identified through the tumor registry of a pediatric hospital and matched controls (n = 193) through random digit dialing. In addition to parental occupational histories, telephone interviews elicited information about potential confounders and hypothesized risk factors for childhood brain tumors. Relying primarily on the Hoar et al. (J Occup Med 1980;22:722-6) job-exposure matrix, the authors examined parental employment characteristics in relation to the relevant developmental periods. Paternal employment in several industries (agriculture, construction, metal, and food and tobacco) and in several occupations (agriculture, benchwork, and transportation) was associated with excess risk. The range of notably elevated odds ratios was 2.0-3.3, with all confidence intervals including 1.0 except one. Elevated but unstable odds ratios were also found for both paternal and maternal employment in jobs "clustered" together because of common exposures. For both approaches to exposure classification, the greatest excess risks were consistently demonstrated for parental jobs held in the preconception period. Job-exposure matrix analyses indicated that case fathers were more likely than control fathers to have had jobs linked with aromatic amino and aromatic nitro compounds (range of notably elevated (and unstable) odds ratios, 3.4-4.4), but here the greatest excess risks were exhibited in the postnatal period. Few associations emerged for maternal employment characteristics, although this is probably explained by the relatively small number of women employed in jobs outside the home.

Adolescent↗
PubMed2004

p-Nitrophenyl isocyanide.

Achiral p-nitrophenyl isocyanide, C(7)H(4)N(2)O(2), crystallizes in the orthorhombic chiral space group P2(1)2(1)2(1). Attractive intermolecular interactions between the nitro O atoms and both aromatic H and nitro N atoms of neighbouring molecules are observed. The O.N interaction is surprisingly strong [N.O = 2.869 (2) A] compared with other aromatic nitro compounds.

Journal Article↗