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 361 records · Page 20Linked to original sources
PubMed1979

The metabolic fate of cholesterol-5 alpha, 6 alpha-expoxide in vivo.

[14C] Cholesterol-5 alpha, 6 alpha-expoxide, administered to mice by either gastric intubation or skin painting, was rapidly and primarily excreted in the feces. Residual amonts of the epoxide and its metabolites were found in a wide variety of organs, and persisted for at least 72 hr. At some sites (principally the liver, the small intestinal contents and the combined stomach/duodenum and their contents), the labeled compound existed in a water-soluble form which could not be extracted with chloroform/methanol. Treatment of the small intestinal contents with a preparation of beta-glucuronidase/sulfatase produced a marked increase in the amount of organic-solvent-extractable cholesterol-alpha-epoxide and other polar metabolites. Unchanged epoxide was found mainly in the feces and the skin at the site of application. On the basis of these results, stool specimens, and not blood samples, should be analyzed to detect the presence of this compound and/or its metabolites in vivo.

Administration, Topical↗
PubMed1991

Comparative metabolism of cannabidiol in dog, rat and man.

Urinary metabolites of cannabidiol (CBD) were extracted from human, dog and rat urine, concentrated by chromatography on Sephadex LH-20, and identified by GC/MS. Over 50 metabolites were identified with considerable species variation. CBD was excreted in substantial concentration from human urine, both in the free state and as its glucuronide. In dog, unusual glucoside conjugates of three metabolites (4''- and 5''-hydroxy and 6-oxo-CBD), not excreted in the unconjugated state, were found as the major metabolites at early times after drug administration. Other metabolites in all three species were mainly acids. Side-chain hydroxylated derivatives of CBD-7-oic acid were particularly abundant in human urine but much less so in dog. In the latter species the major oxidized metabolites were the products of beta-oxidation with further hydroxylation at C-6. A related, but undefined pathway, resulted in loss of three carbon atoms from the side-chain of CBD in man with the production of 2''-hydroxy-tris,nor-CBD-7-oic acid. Previous experiments indicate that 3'-hydroxy-metabolites are the precursors of compounds having this side-chain. Metabolism by the epoxide-diol pathway, resulting in dihydro-diol formation from the delta-8-double bond, gave metabolites in both dog and human urine. It was concluded that CBD could be used as a probe of the mechanism of several types of biotransformation, particularly those related to carboxylic acid metabolism, as intermediates of the type not usually seen with endogenous compounds were excreted in substantial concentration.

Animals↗
PubMed1987

Glycidol-modified gels for molecular-sieve chromatography. Surface hydrophilization and pore size reduction.

Divinyl sulfone-crosslinked agarose gels were made hydrophilic by coupling glycidol to the agarose chains. The concentration of glycidol in the reaction mixture determines the pore size of the gels (the glycidol molecules probably form polymers, the degree of polymerization increasing with the glycidol concentration). Gels prepared with moderate glycidol concentrations are still porous enough to be used for separation of proteins and peptides. Gels with a high degree of glycidol polymerization are suited for desalting of low-molecular-weight compounds, for instance peptides.

1-Propanol↗
PubMed1978

Mutagenicity of aliphatic epoxides.

The mutagenicity of 17 aliphatic epoxides was determined using the specially constructed mutants of Salmonella typhimurium developed by Ames. The activity of these epoxides together with those reported in the literature as mutagens in strains TA100 and TA1535 depended on the degree of substitution around the oxirane ring. Monosubstituted oxiranes were the most potent mutagens in both strains. 1,1-Disubstitution resulted in the complete loss or reduction of mutagenicity, trans-1,2-Disubstituted, and tetrasubstituted oxiranes all lacked mutagenicity, while the cis-1,2-disubstituted oxiranes tested were weakly mutagenic in strain TA100 only. For the monosubstituted compounds the presence of electron-withdrawing substituents increased mutagenicity.

Epoxy Compounds↗
PubMed1990

DNA strand breaks in liver for four aliphatic epoxides in mice.

Four aliphatic epoxides, 1-naphthyl glycidyl ether (NGE), 1-naphthylpropylene oxide (NPO), 4-nitrophenyl glycidyl ether (NPGE), 3,3,3-trichloropropylene oxide (TCPO) and two of their precursors, 1-allylnaphthalene (AN) and 3,3,3-trichloropropylene (TCP), were selected for DNA strand-break analysis in liver in vivo with mice. The four epoxides selected were among the most mutagenic aliphatic epoxides in our previous structure-mutagenicity studies with the Ames test and had been evaluated for their in vivo genotoxicity as measured by sister-chromatid exchange (SCE) and chromosome aberrations (CA). A significant increase in the percentage of unwound DNA was observed at a 4-h exposure time for all the compounds at high doses except for AN. TCPO, the least genotoxic compound in bone marrow, had the greatest liver toxicity after 1-h exposure while NGE showed the most toxicity after 6 h. As might be expected from their corresponding epoxides, AN but not TCP exhibited significant SCE activity in the bone marrow of mice. This study reemphasizes the importance of evaluating the stability of direct-acting alkylating agents in comparing test results and in establishing the relative order of genotoxicity for such compounds.

Animals↗
PubMed2005

Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 A resolution: structure-activity relationships in epoxides inhibiting EH activity.

Homology modelling of the human microsomal epoxide hydrolase (EH) enzyme based on the fungal (Aspergillus niger) EH crystallographic template is reported. The active site lies in a well-defined, essentially hydrophobic, pocket within the overall enzyme structure. Two tyrosine residues, that are conserved in all known mammalian EH sequences, are able to form hydrogen bonds (one per tyrosine residue) with the epoxide oxygen atom on the known EH substrate, styrene oxide. There is also a small hydrophobic cleft, within the active site region, where the phenyl group of styrene oxide can bind, but this appears to be restricted such that the presence of bulky side-chains will render poor substrate status to the incoming epoxide molecule. Quantitative structure-activity relationship (QSAR) studies on a series of low molecular weight epoxides provide useful results which appear to be generally consistent with the human microsomal EH model, and thus may be used predictively for assessing the EH substrate and/or inhibitor status of untested compounds.

Animals↗
PubMed2001

Syntheses of 5a'-homo-vinblastine and congeners designed to establish structural determinants for isolation of atropisomers.

The syntheses of 5a'-homo-vinblastine (3a) and its C-20' methyl congener 62a were achieved. In contrast to vinblastine, these compounds did not allow isolation of atropisomers because of their lower conformational inversion barrier. However, annelation of a six-membered ring to the conformationally mobile D'-piperidine ring provided an isolated atropisomer 81a, which could be converted to its lower energy conformation 65a on heating. The 5a'-homo-vinblastine congeners 3a, 62a, and 65a showed vinblastine-like inhibition of tubulin polymerization and cytotoxicity to L1210 leukemia cells, albeit at lower potency for the latter activity, than that found with the corresponding compounds in the vinblastine series.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Flanking sequences modulate diepoxide and mustard cross-linking efficiencies at the 5'-GNC site.

Diepoxybutane, diepoxyoctane, and mechlorethamine are cytotoxic agents that induce interstrand cross-links between the N7 positions of deoxyguanosine residues on opposite strands of the DNA duplex preferentially at 5'-GNC sequences. We have systematically varied the identity of either the base 5' to the cross-linked deoxyguanosine residues or the intervening base pair to determine flanking sequence effects on cross-linking efficiency. We used synthetic DNA oligomers containing four 5'-N(1)GN(2)C sites that varied either N(1) or N(2). Interstrand cross-links were purified through denaturing polyacrylamide gel electrophoresis and then subjected to piperidine cleavage. The amount of cleavage at each deoxyguanosine residue, representative of cross-linking efficiency at that site, was determined by sequencing gel analysis. Our data suggest that cross-linking efficiency varies with the identity of N(1) similarly (purines > pyrimidines) for diepoxybutane, diepoxyoctane, and mechlorethamine but that the effects of N(2) differ for the three compounds.

Base Sequence↗
PubMed1978

Contaminants in human milk.

There is a paucity of information regarding excretion of contaminants in human milk, due to experimental difficulties and until recently a general lack of interest. Because of the high fat content of milk and as its acidity is higher than that of plasma, nearly all liposoluble and basic agents consumed by the mother will be excreted in the milk. Distinction must be made between, on the one hand drugs and social toxicants such as smoking and alcohol, whose intake can be stopped or limited during pregnancy and lactation, and ecological toxicants present in a polluted environment to which the mother is exposed. Cases have occurred of heavy prenatal and postnatal intoxication of infants with hexachlorobenzene in Turkey and methylmercury in Iraq due to consumption of fungicide-treated seed wheat by pregnant and lactating mothers. Recent attention has been concentrated on contamination of milk with organochlorine compounds such as DDT and PCB's, that are found in many parts of the world. The heaviest contamination with DDT has been found in Guatemala, resulting in suckling infants consuming many times the Acceptable Daily Intake of this compound proposed by WHO, with unknown future effects.

DDT↗
PubMed2002

Sevelamer, a phosphate-binding polymer, is a non-absorbed compound.

OBJECTIVE: To examine the absorption, distribution and excretion of sevelamer hydrochloride in rats and humans. PARTICIPANTS: Twelve male Sprague-Dawley rats were used in the animal study, and twenty human volunteers participated in the clinical trial. METHODS: In the animal study, six rats received a single oral dose of [(3)H]sevelamer and six rats were pretreated with unlabelled sevelamer in the diet for 28 days followed by a single dose of [(3)H]sevelamer on day 29. Total urine and faeces were collected at intervals up to 72 hours post dose, and tissues were obtained at the time of sacrifice. In the clinical trial, subjects received a single oral dose of [(14)C]sevelamer following 28 days of pretreatment with unlabelled sevelamer. Blood, urine and faeces samples were collected at intervals up to 96 hours. RESULTS: In the rat study, no significant urinary excretion of radioactivity was observed. The average recovery of radioactivity in the faeces was 98% in the single-dose group and greater than 100% in the group pretreated with unlabelled sevelamer for 28 days. A total of less than 0.1% of the dose was found in the tissues. In the human study, no detectable amount of (14)C was found in the blood of any subject at any time. The majority of subjects had no detectable amounts of (14)C recovered in the urine. In subjects where (14)C was recovered in the urine, less than 0.02% was detected, a level equivalent to the free (14)C detected in the [(14)C]sevelamer preparation. On average, greater than 99% of the administered dose was recovered in the faeces of the subjects. CONCLUSION: These studies demonstrate that sevelamer is a non-absorbed compound.

Absorption↗
PubMed2006

Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss.

Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.

Adipocytes↗
PubMed1999

Time-related bisphenol-A content and estrogenic activity in saliva samples collected in relation to placement of fissure sealants.

It was recently reported that estrogenic activity was detected in saliva samples collected during 1 h after placement of one fissure sealant (Delton) and this related to Bisphenol-A (BPA) content. The aim of the present study was to determine the time-related BPA content and estrogenic activity in saliva samples collected before and after placement of two fissure sealants each with a different monomer composition. Eight healthy male volunteers with no history of prior placement of fissure sealants or composite resin fillings had four molars sealed with either Delton LC (four people) or Visio-Seal (four people). Base-line saliva samples were collected preexperimentally, in the morning when fasting. Fissure sealants were placed and saliva samples collected immediately, 1 h and 24 hs after placement of the fissure sealant. BPA was found in saliva samples collected immediately after placement of Delton LC (range 0.3-2.8 ppm). No detectable amounts of BPA were determined 1 h and 24 h after Delton treatment (detection limit < or = 0.1 ppm). In base-line samples and in all samples collected from Visio-Seal treated individuals, no BPA was detected. In a recombinant yeast cell assay, significantly increased estrogenic activity was found in saliva samples collected immediately after placement of Delton LC sealant (P < 0.05; ANOVA) whereas no statistically significant estrogenic activity was observed in the remaining groups. In conclusion, minute amounts of BPA, however considerably lower than previously reported, were detected in saliva samples collected immediately after but not 1 and 24 h(s) after placement of Delton LC fissure sealant. BPA was not detected after placement of Visio-Seal fissure sealant.

Adult↗
PubMed2006

PPARgamma antagonists reverse the inhibition of neural antigen-specific Th1 response and experimental allergic encephalomyelitis by Ciglitazone and 15-deoxy-Delta12,14-prostaglandin J2.

Peroxisome proliferator-activated receptor-gamma is a nuclear receptor transcription factor that regulates cell growth, differentiation and homeostasis. PPARgamma agonists have been used to treat obesity, diabetes, cancer and inflammation and recent studies have shown the protective effects of PPARgamma agonists on experimental allergic encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). Our studies have further demonstrated that the PPARgamma agonists, 15d-PGJ2 and Ciglitazone, inhibit EAE through blocking IL-12 signaling leading to Th1 differentiation and the PPARgamma deficient heterozygous mice (PPARgamma+/-) or those treated with PPARgamma antagonists develop an exacerbated EAE in association with an augmented Th1 response. In this study, we show that the PPARgamma antagonists, Bisphenol A diglycidyl ether (BADGE) and 2-chloro-5-nitro-N-(4-pyridyl)benzamide (T0070907), reverse the inhibition of EAE by the PPARgamma agonists, Ciglitazone and 15-Deoxy-Delta(12,14)-Prostaglandin J2, in C57BL/6 wild-type and PPARgamma+/- mice. The reversal of EAE by BADGE and T0070907 was associated with restoration of neural antigen-induced T cell proliferation, IFNgamma production and Th1 differentiation inhibited by Ciglitazone and 15d-PGJ2. These results suggest that Ciglitazone and 15d-PGJ2 ameliorate EAE through PPARgamma-dependent mechanisms and further confirm a physiological role for PPARgamma in the regulation of CNS inflammation and demyelination in EAE.

Animals↗
PubMed2001

Synthesis and biochemical investigation of scyphostatin analogues as inhibitors of neutral sphingomyelinase.

The sphingolipid ceramide is considered to be an important intracellular mediator. However, many aspects of its action and the role of several different ceramide generating sphingomyelinases are still unclear. Recently, we reported on the synthesis of the first selective irreversible inhibitor of the neutral sphingomyelinase (N-SMase), as well as the identification of Manumycin A and some of its analogues as irreversible inhibitors of N-SMase. For the development of pharmacologically interesting competitive inhibitors of N-SMase, structure-activity studies are essential. Herein we show the synthesis and enzymatic investigation of two scyphostatin analogues 3a and 3b, revealing the importance of the primary hydroxy group in compound 2 for N-SMase inhibition.

Amides↗
PubMed2002

Role of the azinomycin naphthoate and central amide in sequence-dependent DNA alkylation and cytotoxicity of epoxide-bearing substructures.

Studies report a strong correlation between duplex DNA alkylation and in vitro cytotoxicity for a series of azinomycin partial structures 2-6 bearing the biologically relevant epoxide. Compounds lacking the naphthoate ester (e.g., 5 and 6) were poorly reactive toward DNA and were biologically inactive, as were compounds bearing the naphthoate but lacking the terminal carboxamide (e.g., 2). Compounds were evaluated for cytotoxicity against two breast cancer cell lines. [structure: see text]

Alkylation↗
PubMed1999

Sets of aldolase antibodies with antipodal reactivities. Formal synthesis of epothilone E by large-scale antibody-catalyzed resolution of thiazole aldol.

[formula: see text] Three monoclonal aldolase antibodies, generated against a beta-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions of ent-8a-k, providing optically pure 8a-k by kinetic resolution. Compounds (+/-)-8a, (+/-)-8g, and (+/-)-8k have been resolved in multigram quantities using 0.003, 0.005, and 0.0004 mol% antibody catalysts, respectively. Resolved compounds 8a-k are useful synthons for the construction of epothilones A-E (2-6) and their analogues. Here, a formal synthesis of epothilone E, 6 has been achieved starting from compound 8g.

Antibodies, Catalytic↗
PubMed2000

A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation.

While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPARgamma with a K(d(app)) of 100 microM. This compound has no apparent ability to activate the transcriptional activity of PPARgamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPARgamma activity is required for the hormonally induced differentiation of adipogenic cells.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Effects of tetraethyl lead on the activities of drug metabolizing enzymes in different tissues of the rat.

The present study describes the effects of tetraethyl lead on various drug metabolizing enzymes in different tissues of the rat. Tetraethyl lead was administered intraperitoneally to rats (250 mumol/kg) on two consecutive days. The animals were killed on day 3. Tetraethyl lead-treatment decreased the concentration of hepatic cytochrome P-450 (to 45 per cent of the control), the hepatic activity of aryl hydrocarbon hydroxylase (to 41 per cent of the control) and ethoxycoumarin deethylase (to 45 per cent of the control). Epoxide hydratase activity was enhanced in the liver (1.3-fold), kidney (3.3-fold), and small intestinal mucosa (4.7-fold). The activity of glutathione S-transferase decreased in the liver (to 69 per cent of the control) but increased in the kidney (1.5-fold) and small intestinal mucosa (1.7-fold). The glucuronidation of o-aminophenol was enhanced (2.2-fold) in the kidney of tetraethyl lead treated rats. It is concluded that exposure to tetraethyl lead brings about widespread changes in the ability of mammals to detoxify foreign compounds.

Animals↗