Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Epoxy Compounds”

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 865 records · Page 48Linked to original sources
PubMed1990

Chromosomal aberrations and micronuclei in lymphocytes in relation to alkylation of hemoglobin in workers exposed to ethylene oxide and propylene oxide.

Chromosomal aberrations and micronuclei in lymphocytes were measured in workers exposed to propylene oxide in a factory producing alkylated starch, and in workers exposed to ethylene oxide in connection with sterilization of medical equipment. Adduct levels in hemoglobin were determined as a measure of in vivo doses of the two compounds. The levels of hydroxypropylvaline in propylene oxide-exposed workers were correlated in estimated exposure doses. The levels of this adduct in the unexposed group were close to the detection limit of the method. The levels of hydroxyethylvaline, recorded in the propylene oxide-exposed group were consistent with earlier data on hemoglobin alkylation in occupationally unexposed subjects. The adduct measurements revealed increased levels of hydroxyethylvaline in the two subgroups of ethylene oxide-exposed workers, i.e., assemblers with a low and sterilizers with a high exposure. According to expectation the subgroups differed in adduct levels. The results of the cytogenetic study showed that the clastogenic potency of propylene oxide was lower than that of ethylene oxide, since the propylene oxide-exposed individuals had lower frequencies of micronuclei and chromosomal breaks compared to the assemblers despite a lower adduct level in the last group.

Adult↗
PubMed1985

Inhibition of epoxide metabolism by alpha,beta-epoxyketones and isosteric analogs.

Chalcone oxides and several isosteric compounds have been prepared to examine the importance of the alpha,beta-epoxyketone moiety in the inhibition of the hydrolysis of [3H]-trans-stilbene oxide to its meso-diol by mouse liver cytosolic epoxide hydrolase (cEH). Inhibition of microsomal EH and glutathione S-transferase were also examined. For cEH, replacement of the carbonyl by methylidene reduces inhibitor potency by a factor of 44, while replacement of the epoxide ring with a cyclopropyl ring reduces inhibition by a factor of 450. A 2'-hydroxyl also reduces cEH inhibition by 100 times. These observations are consistent with a model of the active site in which the carbonyl is hy-hydrogen-bonded to an acidic site presumed to be involved in initiating epoxide hydrolysis. The chalcone oxides thus bind tightly but are not readily turned over as substrates.

Animals↗
PubMed1995

The genotoxicity of benzanthracenes: a quantitative structure-activity study.

Molecular orbital (MO) evaluations of a series of 14 methyl-substituted benz[alpha]anthracenes, calculated by the complete neglect of differential overlap (CNDO/2) method, are reported. By quantitative structure-activity relationship (QSAR) analysis, the carcinogenic and mutagenic potencies of these compounds have been shown to be correlated with their electronic structures, namely, with the magnitude of the energy of the lowest unoccupied molecular orbital (LUMO). The log mutagenicity potencies for the series of 14 benz[alpha]anthracenes are negatively dependent on E(LUMO), with a correlation coefficient of 0.82, which is increased to 0.90 by inclusion in the QSAR of a second variable, namely Q3H, the electronic density in the highest occupied molecular orbital, E(HOMO), of carbon-3. E(LUMO) is also negatively correlated with mouse carcinogenicity of the benzanthracenes, with a correlation coefficient of 0.88 for tumour incidence, and of 0.83 for log carcinogenicity index. The carcinogenicity and mutagenicity of the individual members of this series of polycyclic aromatic hydrocarbons are discussed in terms of the relationships between molecular structure, electron density, metabolic activation and covalent binding of reactive intermediates.

Animals↗
PubMed2002

Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal alpha-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities.

Apicidins are a class of cyclic tetrapeptides that do not contain the classical electrophilic alpha-keto epoxide yet are potent (nM) inhibitors of histone deacetylase and antiprotozoal agents. These compounds showed broad-spectrum activities against the apicomplexan family of protozoa including Plasmodium sp (malarial parasite), Toxoplasma gondii, Cryptosporidium sp., and Eimeria sp. These cyclic peptides contain a beta-turn amino acid (R)-Pip or (R)-Pro, (S)-N-methoxy Trp, (S)-Ile, or (S)-Val, and either (S)-2-amino-8-oxodecanoic acid or a modified (S)-2-amino-8-oxodecanoic acid. The isolation and structure elucidation of new apicidins from two Fusarium species, temperature-dependent NMR studies of apicidin, NMR and molecular modeling based conformation of the 12-membered macrocyclic ring, and selected chemical modifications of apicidin have been detailed in this paper. The cyclic nature of the peptide, the C-8 keto group, and the tryptophan are all critical for the biological activity.

Antiprotozoal Agents↗
PubMed1984

Chemical models for toxic metabolites of bromobenzene derivatives. Relative toxicity toward isolated hepatocytes.

In the rat the hepatotoxicity of bromobenzene is greatly enhanced by the introduction of a cyano group adjacent to the bromine (i.e. o-bromobenzonitrile). Epoxide metabolites of these aryl halides are believed to be the actual toxic species, but epoxides of the latter compound also possess a second site of chemical reactivity not found in epoxides of bromobenzene, i.e. a Michael acceptor group formally related to acrylonitrile. Because these epoxides have never been isolated or synthesized for direct evaluation of their toxicity we have determined the toxicity toward isolated rat hepatocytes of a series of cyclohexene and cyclohexadiene derivatives containing epoxide and/or alpha, beta-unsaturated nitrile functional groups. Simple epoxides and unsaturated nitriles were much less toxic than bromobenzene itself, even if both groups were present in the same molecule. However, alpha, beta-unsaturated epoxides were found to be 2-3 times more toxic than bromobenzene, and at least 10 times more toxic than their saturated analogs, which is consistent with their relatively greater chemical reactivity. It is unlikely that Michael acceptor metabolites account for the increased toxicity of o-bromobenzonitrile relative to bromobenzene.

Alanine Transaminase↗
PubMed1997

Changes in high molecular weight DNA fragmentation following human blood exposure to styrene-7,8-oxide.

Styrene-7,8-oxide (S7,8O) is the major in vivo metabolite of styrene and is a genotoxic agent potentially carcinogenic to humans. It is known to cause DNA strand breaks and adducts. We studied high molecular weight DNA fragmentation in white blood cells following incubation of blood with S7,8O from individuals with no previous exposure to this compound. To better understand the effects of S7,8O, we also examined blood exposed to hydrogen peroxide (H2O2) a typical oxidant that is linked to oxidative stress. All individuals in this study showed a variable reduction in high molecular weight DNA fragments determined by laser densitometry compared to untreated controls for both S7,8O and H2O2 treated samples. This decrease was independent of the concentration and length of exposure of blood to S7,8O and H2O2. An increase in low molecular weight DNA fragments from samples treated with S7,8O and H2O2, compared to untreated samples was also noted. Similarities in the reduction of HMW-DNA fragments after S7,8O and H2O2 exposure suggested a similar mechanism of HMW-DNA damage. It was surmised that S7,8O exposure in blood may induce high molecular weight DNA fragmentation due to oxidative stress.

Carcinogens↗
PubMed1996

Isolated colophony allergens as screening substances for contact allergy.

Rosin has a complex chemical composition. The aim of this study was to investigate if it is possible to define 1 or 2 compounds as the rosin allergens. 2 compounds, 13, 14(beta)-epoxyabietic acid and 7-oxodehydroabietic acid, identified in gum rosin and tall oil rosin, were used as screening substances for patch testing in addition to the standard series. The rosin patch detected more cases of contact allergy than the isolated allergens did. Our suggestion is to patch test with a preparation of gum rosin, as well-defined as possible, for screening. The content of oxidation products should be kept at a constant and rather high level, since these are the main allergens. A rosin series for additional testing of patients with allergic contact dermatits suspected to be caused by rosin could be a valuable tool. Gum rosin and tall oil rosin from different countries should be included, since the amounts of allergens in rosin varies due to source and mode of production. Testing with identified allergens from modified rosin products and with modified rosins could also be performed.

Abietanes↗
PubMed1975

Structural effects on the reactivity of substrates and inhibitors in the epoxidation system of Pseudomonas oleovorans.

The epoxidation reaction catalyzed by an enzyme system of Pseudomonas oleovorans exhibits a substrate specificity different from that expected on the basis of chemical reactivity in non-enzymatic epoxidation reactions. Cyclic and internal olefins, aromatic compounds and styrene are not epoxidated. The reactivity of straight chain diolefins is maximal for octadiene and falls off rapidly as the carbon chain is shortened, but decreases only slightly as the chain is lengthened. In contrast, methyl group hydroxylation is less sensitive to decreasing chain length. As a consequence, propylene and 1-butene are hydroxylated but not epoxidated by this enzyme system. With the substrate 1-decene, which is capable of undergoing both epoxidation and hydroxylation, the former reaction predominates. Methyl imidoesters were found to be inhibitors of enzymatic epoxidation, and the potency of a homologous series of imidoester inhibitors was examined. The results parallel the substrate specificity patterns observed, and support the conclusion that the mode of substrate binding severely moderates the inherent chemical reactivity of the activated oxygen in this system. The effect of the bifunctional imidoester, dimethyladipimidate, was also examined and the results compared with those obtained in other investigations.

Alcohols↗
PubMed2003

Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE2.

The major physiological inhibitors of insulin secretion, norepinephrine, somatostatin, galanin, and prostaglandin E2, act via specific receptors that activate pertussis toxin (PTX)-sensitive G proteins. Four inhibitory mechanisms are known: 1) activation of ATP-sensitive K channels and repolarization of the beta-cell; 2) inhibition of L-type Ca2+ channels; 3) decreased activity of adenylyl cyclase; and 4) inhibition of exocytosis at a "distal" site in stimulus-secretion coupling. We have examined the underlying mechanisms of inhibition at this distal site. In rat pancreatic islets, 2-bromopalmitate, cerulenin, and polyunsaturated fatty acids, all of which suppress protein acyltransferase activity, blocked the distal inhibitory effects of norepinephrine in a concentration-dependent manner. In contrast, control compounds such as palmitate, 16-hydroxypalmitate, and etomoxir, which do not block protein acylation, had no effect. Furthermore, 2-bromopalmitate also blocked the distal inhibitory actions of somatostatin, galanin, and prostaglandin E2. Importantly, neither 2-bromopalmitate nor cerulenin affected the action of norepinephrine to decrease cAMP production. We also examined the effects of norepinephrine, 2-bromopalmitate, and cerulenin on palmitate metabolism. Palmitate oxidation and its incorporation into lipids seemed not to contribute to the effects of 2-bromopalmitate and cerulenin on norepinephrine action. These data suggest that protein acylation mediates the distal inhibitory effect on insulin secretion. We propose that the inhibitors of insulin secretion, acting via PTX-sensitive G proteins, activate a specific protein acyltransferase, causing the acylation of a protein or proteins critical to exocytosis. This particular acylation and subsequent disruption of the essential and precise interactions involved in core complex formation would block exocytosis.

Acylation↗
PubMed2005

Evidence for the preventive effect of the polyunsaturated phytol side chain in tocotrienols on 17beta-estradiol epoxidation.

BACKGROUND: We found that 17beta-estradiol (E2) could be activated by epoxidation to bind DNA and to inhibit nuclear RNA synthesis. Vitamin E compounds are powerful antioxidants and chain-breaking free radical scavengers. The chromanol ring in Vitamin E is believed to be involved in these reactions. METHODS: Here, we examined the preventive effect of alpha-tocopherol, alpha-, gamma- and delta-tocotrienols on E2 activation. RESULTS: We found that when any one of these Vitamin E compounds was mixed with E2 for epoxidation by the epoxide-forming oxidant dimethyldioxirane (DMDO), alpha-tocopherol was the least effective as compared with the tocotrienols against the formation of E2 epoxide as reflected by the loss of the ability of E2 to inhibit nuclear RNA synthesis. This conclusion was further confirmed by the binding studies of [3H] labeled E2 to DNA using either DMDO or liver microsomes activation system. CONCLUSIONS: Since the chromanol ring is shared by both tocopherols and tocotrienols and the only difference between these two subgroups of Vitamin E is the phytol side chain, we conclude that the polyunsaturated phytol group in tocotrienols plays a key preventive role in E2 epoxidation. This is the first report showing that the polyunsaturated phytol side chain in tocotrienols is involved in an antioxidative activity and it may also have a preventive effect against the E2 epoxide induced breast cancer carcinogenesis at the initiation.

Animals↗
PubMedDate not supplied

Crosslinkage of collagen by polyglycidyl ethers.

Calcification is the principal cause of failure of glutaraldehyde treated bioprosthetic heart valves. This article reports the crosslinkage of several polyglycidyl ethers. Calcification of yak pericardium with polyglycidyl ethers was significantly decreased compared with that crosslinked with glutaraldehyde. The process of calcification of crosslinked yak pericardium was studied using 21 day subdermal implants in rats. The uptake of calcium with ethane diglycidyl ether was reduced (0.57 +/- 0.19 vs 4.28 +/- 1.62 micrograms/mg) over that with glutaraldehyde. Four polyglycidyl ethers were developed and compared. The best compound for raising the shrinkage temperature was the shortest chain compound without steric hindrance. In the polyglycidyl ether process, a suitable amount of alcohol was necessary to promote crosslinking; the catalyst, 2, 4, 6 -tris (dimethyl aminomethyl) phenol (TDAMP) and salicylic acid, were not favorable for long-term treatment of tissues because of the unnecessarily deep dyeing of the tissue, in addition to raising the shrinkage temperature. Unlike glutaraldehyde treatment, which reacts with lysine, polyglycidyl ether treated tissues maintained flexibility of the pericardial tissue, while binding amino acids such as lysine, methionine, tyrosine, aspartic acid and glutamic acid. The authors conclude that the ethane diglycidyl ether process combined with formaldehyde would further raise the shrinkage temperature from 78 degrees C to 87.5 degrees C and sustain it above 80 degrees C. Reverse treatment was not as effective. Compared with glutaraldehyde, polyglycidyl ether treatment renders tissue more flexible, increases the thermal stability of collagen, and decreases the incidence of calcification in vivo.

Amino Acids↗
PubMed1989

Modification of an essential arginine residue associated with the plasma membrane ATPase of red beet (Beta vulgaris L.) storage tissue.

The dicarbonyl compounds, phenylgloxyl and 2,3-butanedione were used to demonstrate the presence of an essential arginine residue in the mechanism of the red beet (Beta vulgaris L.) plasma membrane ATPase. Treatment of the red beet ATPase with either of these reagents resulted in an inhibition of ATP hydrolytic activity protectable by the inclusion of either ATP or ADP during inhibitor incubation. Ligands of the ATP hydrolytic reaction also protected against phenylglyoxyl inhibition and affected the ability of ADP to protect against inhibition by this reagent. Kinetic analysis of 2,3-butanedione and phenylglyoxyl inhibition suggested the presence of a single arginine residue susceptible to attack by these reagents. As similar results with these arginine modification reagents were found for both the plasma membrane-associated and solubilized forms of the ATPase, it is apparent that the function of this arginyl moiety is not affected by detergent treatment and removal of the enzyme from the membrane.

Adenosine Diphosphate↗
PubMed2005

T(H1)-directed modulation of in vitro cytokine production in human peripheral blood mononuclear cells by styrene-7.8-oxide.

Styrene and its chiral main metabolite styrene-7.8-oxide are well characterized regarding their cytotoxic, genotoxic and neurotoxic properties. To our knowledge, no data exist on the influence of styrene and styrene-7.8-oxide on immune reactions. Epidemiological studies suggest that exposure to environmental pollutants, specifically volatile organic compounds (VOCs), including styrene is one factor contributing to increasing prevalence rates of allergic diseases. In this study, we investigated the modulation of the immune system by styrene-7.8-oxide in vitro. Human peripheral blood mononuclear cells were incubated with styrene-7.8-oxide, either as (S)-enantiomer, (R)-enantiomer, or racemic styrene-7.8-oxide. Subsequently, the secretion of T(H1)-cytokines IFNgamma and IL-12 as well as T(H2)-cytokines IL-4 and IL-5 were measured by ELISA. We introduced a novel mathematical approach to quantify and compare cytokine responses. The results revealed a stimulation of cytokine secretion with emphasis on T(H1)-cytokines IFNgamma and IL-12. The stimulating effects were elicited at concentrations of styrene-7.8-oxide comparable to what would be encountered at industrial workplaces where styrene is processed. Therefore, we conclude that styrene-7.8-oxide exhibits immunomodulating capacities, which can be of clinical relevance for individuals with high styrene exposure.

Air Pollutants, Occupational↗
PubMedDate not supplied

Sterilization of a small caliber vascular graft with a polyexpoxy compound.

Sterilization of tissue based medical devices via cold sterilization processes has been limited to formaldehyde, glutaraldehyde, and mixtures of the same with alcohols and surfactants. The authors report the sterilization of a small caliber vascular graft with a combination of diglycidyl ether and ethanol. The sterilant contains 1-4% diglycidyl ether and 10-20% ethanol as an aqueous solution. Sterilization is achieved after exposure of the graft to the sterilant solution for a period of 7 days at an elevated temperature (30 degrees - 40 degrees C). The biologic indicator selected for efficacy studies was Bacillus subtilis niger ATCC 9372 (endospores). The grafts were inoculated with a concentrated endospore suspension and immersed in the sterilant solution for increasing time periods. After extensive rinsing over membrane filters to remove any residual sterilant, the grafts and filters were cultured in tryptic soy broth. D10 values were calculated using a fraction-negative, most probable number technique. Additionally, many representative bacteria and fungi were tested and found to be susceptible to the new sterilant developed. The diglycidyl ether/alcohol sterilant developed was found to be efficacious for sterilization of the tissue based vascular grafts tested.

Bacteria↗
PubMed1986

Reactivity of mutagenic propylene oxides with deoxynucleosides and DNA.

In an extension of previous studies with deoxycytidine and thymidine reactivities, propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide were reacted with deoxyguanosine as well as deoxyadenosine and, except for the trichloro compound, with DNA. Reactivity with the purine deoxynucleosides as well as the four deoxynucleosides in DNA were quantitated by HPLC methods. Correlations were found for the reactivity with individual deoxynucleosides in solution to Taft sigma electron-withdrawing values of the substituents on the epoxides and for reaction with model nucleophiles. In general, these correlations were not as pronounced for the reactivities of the propylene oxides with the nucleosides in DNA. Correlations for reactivity of the propylene oxides with the individual deoxynucleosides in solution and in DNA, except for dThd, were indicated for mutagenicity in TA100 in the liquid-preincubation Ames test. However, this was not the case for mutagenicities determined with the plate incorporation procedure nor with TA1535, where the relative mutagenicity of trichloropropylene oxide was the outstanding difference. Trichloropropylene oxide appeared to depend upon the error-prone system in TA100 for full expression of its mutagenicity.

Alkylation↗
PubMed2001

Synthesis and characterization of nucleosides and oligonucleotides bearing adducts of butadiene epoxides on adenine n(6) and guanine n(2).

Butadiene is a major industrial chemical whose genotoxic effects are attributed to the reaction of its oxidized metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2), with DNA. Nucleosides and oligonucleotides containing regio- and stereochemically specific adducts of BDO and the BDO2-related compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine [(2R)- and (2S)-N(2)-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N(2)-(2,3,4-trihydroxybut-1-yl), respectively] and on adenine [(2R)- and (2S)-N(6)-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N(6)-(2,3,4-trihydroxybut-1-yl), respectively] have been prepared by nonbiomimetic routes. For guanine adducts, 2-fluoro-O(6)-(trimethylsilylethyl)-2'-deoxyinosine was treated with (2R)- and (2S)-2-amino-3-buten-1-ol to give the BDO adducts and with (2R,3R)- and (2S,3S)-1-amino-2,3,4-butanetriol to produce the BDE adducts; the adducted oligonucleotides were prepared from 11-mer oligonucleotides containing the halopurine. Adenine adducts were prepared in a similar fashion using 6-chloropurine 2'-deoxyriboside as the reactive purine component.

Adenine↗
PubMed1993

Recirculating, retrograde heart perfusion according to the Langendorff method for evaluation of MTG--methyl-2-tetradecylglycidate, McNeil 3716--cardiomyopathy.

Recirculating, retrograde heart perfusion according to the Langendorff method was used in an attempt to further elucidate the cardiotoxicity of methyl-2-tetradecylglycidate (McNeil 3716, MTG) and the eccentric hypertrophy elicited by the compound. In subchronic experiments female rats were exposed to MTG 2 x 10 mg/kg and 2 x 25 mg/kg per day for 4 weeks. At various times hearts were perfused ex vivo for up to 2 hr with either 5 mmolar glucose or 0.5 mmolar palmitate as substrate. Substrate uptake (glucose or palmitate) and enzyme release (LDH-lactic dehydrogenase or CPK-creatine-phosphate kinase) were assessed during perfusion. Biochemical analysis (ATP, ADP, AMP, c-AMP, CP, creatine, pyruvate, lactate, glucose-6-phosphate, glycogen, phospholipids, triglycerides and non-esterified fatty acids) were done in hearts before (drug effect) and after perfusion (stress of perfusion). Besides changes in energy metabolism and high-energy phosphate production, as observed in previous experiments (Bachmann et al. 1984) massive changes were seen in energy reserves in heart tissue (ATP, CP, glycogen, phospholipids and triglycerides). As expected, MTG led to significant increases also in non-esterified fatty acids content in hearts.

Adenine Nucleotides↗
PubMed1982

Determination of hydroxypropylhistidine in haemoglobin as a measure of exposure to propylene oxide using high resolution gas chromatography mass spectrometry.

The alkylating agent propylene oxide is a potential carcinogen. Exposure to this compound leads to the formation of N-3'-(2-hydroxypropyl)histidine in protein. A sensitive and specific method has been developed for the determination of this alkylated amino acid in rat and human haemoglobin using high resolution gas chromatography with selected ion monitoring. Globin isolated from blood was hydrolysed with 6 M HCl and the protein hydrolysate chromatographed on a Dowex 50W H+ column. The amino acids in the partially purified extract were analysed as N-heptafluorobutyryl methyl esters using an SE-52 fused silica capillary column. Quantification was made by monitoring the ion m/z 560 [M-COOCH3)+ derived from the derivatized hydroxypropylhistidine in the sample and the corresponding ion at m/z 565 from the pentadeutero analogue of the alkylated amino acid added initially to the globin as an internal standard. The method has been used to quantify hydroxypropylhistidine down to levels of 2 microgram gm-1 haemoglobin and has been applied to studies in rats exposed to propylene oxide.

Animals↗