Activities of hepatic cytosol enzymes involved in UDP-g1ucuronic acid synthesis as well as in glutathione reduction and conjugation systems were determined following administrations of butylated hydroxyanisole (approximately 5 mmol/kg body weight/day) and of equimolar intake doses of its structural anglogs. These compounds included the multi-functional group side chain compounds (t-butyl hydroquinone, 4-hydroxy- anisole, hydroquinone, benzoquinone) and the mono-functional side chain compounds (t-butyl benzene, anisole, phenol). They were administered to mice for 10 days either by mixing them in the diet or by oral intubations. Results showed that glutathione Stransferase activities were markedly increased by all tested compounds except for the t-butyl benzene. Activities of glutathione reductase and glucose 6-phosphate dehydrogenase were increased together on1y by BHA and t-butyl hydroguinone. UDP-glucose dehydrogenase and NADH:quinone reductase activities were significantly elevated by the multi-functional side chain compounds, but not by the mono-functional analogs. The relations between chemical structures of tested BHA analogs and elevations of the measured hepatic cytosol conjugation (detoxification) system enzyme activities for the metabolism and excretion of BHA analogs are discussed.
Animal ; Anisoles/metabolism* ; Butylated Hydroxyanisole/analogs & derivatives ; Butylated Hydroxyanisole/metabolism* ; Cytosol/enzymology* ; Glutathione/metabolism* ; Mice ; Uridine Diphosphate Glucuronic Acid/biosynthesis* ; Uridine Diphosphate Sugars/biosynthesis*

Animals ; Female ; Halogenated Diphenyl Ethers ; Herbicides ; toxicity ; Male ; Mice ; Mice, Inbred Strains ; Mutagenicity Tests ; Phenyl Ethers ; toxicity

Effects of feeding 2(3)-tert-butyl 4-hydroxyanisole (BHA) and 3, 5-di-tert-butyl 4-hydroxytoluene (BHT) on the rates of mixed function oxidation and conjugation enzyme reactions have been determined using isolated hepatic microsomal fractions and isolated perfused livers of mice. The treatments with either of the antioxidants have increased the rates of O-demethylation for p-nitroanisole and of O-deethylation for 7-ethoxycoumarin up to 2-fold, both in microsomes and in perfused liver. Analysis of the perfusate showed that the increased amounts of p-nitrophenol and 7-hydroxycoumarin produced by the elevated mixed-function oxidase activities were reflected by the increase in the amounts of glucuronide conjugates and not in the increase for the amounts of the sulfate ester conjugates. Comparison of results also indicated that in the perfused liver, the maximal rate of metabolite conjugation is limited by the maximal rates of the initial mixed function oxidase activities.
Alkylation ; Animal ; Anisoles/metabolism ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/administration & dosage ; Butylated Hydroxyanisole/pharmacology* ; Butylated Hydroxytoluene/administration & dosage ; Butylated Hydroxytoluene/analogs & derivatives* ; Butylated Hydroxytoluene/pharmacology ; Comparative Study ; Coumarins/metabolism ; Female ; Glucuronosyltransferase/metabolism ; Liver/metabolism* ; Mice ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism* ; Mixed Function Oxygenases/metabolism ; Oxidation-Reduction ; Perfusion ; Support, U.S. Gov't, P.H.S.

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.
Antiviral Agents/pharmacology* ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Illicium/chemistry* ; Phenyl Ethers

Four new diphenyl ethers, named epicoccethers K-N (1-4), were purified from the fermentation medium of a fungus Epicoccum sorghinum derived from Myoporum bontioides, and identified through HR-ESI-MS and NMR spectral analysis. Except that compound 1 showed moderate antifungal activity against Penicillium italicum and Fusarium graminearum, the other three compounds showed stronger activity against them than triadimefon. All of them showed moderate or weak antibacterial activity towards Staphylococcus aureus and Escherichia coli with O6 and O78 serotypes except that 3 was inactive to E. coli O6.
Anti-Bacterial Agents/pharmacology* ; Antifungal Agents/chemistry* ; Ascomycota ; Escherichia coli ; Microbial Sensitivity Tests ; Molecular Structure ; Phenyl Ethers/chemistry*

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.
Animals ; Fingolimod Hydrochloride ; chemical synthesis ; pharmacology ; Heart Rate ; drug effects ; Immunosuppressive Agents ; chemistry ; Lymphopenia ; pathology ; Phenyl Ethers ; chemistry ; Structure-Activity Relationship

Optically active form of alpha-cyano-3-phenoxybenzyl (CPB) alcohol, building block of pyrethroid insecticides, was synthesized as its acetate by the combination of anion-exchange resin (D301)-catalyzed transcyanation between m-phenoxybenzaldehyde (m-PBA) and acetone cyanohydrin (AC), and lipase (from Alcaligenes sp.)-catalyzed enantioselective transesterification of the resulting cyanohydrin with vinyl acetate. Through optimizing technological conditions, the catalyzing efficiency was improved considerably compared to methods previously reported. Concentrations of CPB acetate were determined by gas chromatograph. The enantio excess (e.e.) values of CPB acetate were measured by NMR (nuclear magnetic resonance) method. Effects of solvents and temperatures on this reaction were studied. Cyclohexane was shown to be the best solvent among the three tested solvents. 55 degrees C was the optimal temperature for higher degree of conversion. External diffusion limitation was excluded by raising the rotational speed to 220 r/min. However, internal diffusion could not be ignored, since the catalyst (lipase) was an immobilized enzyme and its particle dimension was not made small enough. The reaction rate was substantially accelerated when the reactant (m-PBA) concentration was as high as 249 mmol/L, but decreased when the initial concentration of m-PBA reached to 277 mmol/L. It was also found that the catalyzing capability of recovered lipase was high enough to use several batches. Study of the mole ratio of AC to m-PBA showed that 2:1 was the best choice. The strategy of adding base catalyst D301 was found to be an important factor in improving the degree of conversion of the reaction from 20% to 80%. The highest degree of conversion of the reaction has reached up to 80%.
Alcaligenes ; enzymology ; Benzaldehydes ; chemistry ; Combinatorial Chemistry Techniques ; methods ; Lipase ; chemistry ; Nitriles ; chemistry ; Organic Chemicals ; chemistry ; Phenyl Ethers ; chemical synthesis ; Technology, Pharmaceutical ; methods

BACKGROUND: The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. METHODS: In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. RESULTS: The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. CONCLUSION: These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.
Animals ; Antibody Formation ; Biphenyl Compounds ; Body Weight ; Cell Proliferation ; Corn Oil ; Enzyme-Linked Immunosorbent Assay ; Ether, Ethyl ; Female ; Halogenated Diphenyl Ethers ; Humans ; Immune System ; Lactation ; Macrophages ; Mice ; Neutrophils ; Phenyl Ethers ; Pregnancy ; Spleen ; Thymocytes ; Thymus Gland

An experiment was conducted in order to investigate the effect of p-dimethylaminoazobenzene (DAB) and 2(3)-tert-butyl-4-hydroxyanisole (BHA) on the lipid peroxidation and peroxide-destroying enzyme system in the rat liver. Dietary supplementation of DAB (0.06%) for three weeks caused the elevation of glutathione-S-transferase activity by 60% and glutathione reductase by 50%, but it decreased glutathione peroxidase and catalase activities significantly. Dietary supplementation of BHA (0.75%) also increased glutatione-S-transferase activity in the liver by 2 folds, and it counteracts DAB effect on the glutathione peroxidase and catalase activities. There was a marked increase in malon-dialdehyde content in the postnuclear fraction of liver by the treatment of DAB, but the addition of BHA lowered the malondialdehyde content to almost the control level. The protective effect of BHA on the lipid peroxidation induced by DAB administration at the enzyme level seems to be due to the induction of glutathione-S-transferase and the protection of glutathione peroxidase and catalase activities from being lowered by DAB administration.
Animal ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/pharmacology* ; Glutathione Peroxidase/analysis* ; Glutathione Reductase/analysis* ; Glutathione Transferase/analysis* ; Lipid Peroxides/metabolism* ; Liver/drug effects* ; Liver/metabolism ; Male ; Peroxidases/analysis* ; Rats ; p-Dimethylaminoazobenzene/pharmacology*

This study was aimed at evaluating the antioxidant activities of methanol extract of Thamnolia vermicularis. The antioxidant activity, reducing power, superoxide anion radical scavenging and free radical scavenging activities were studied. The antioxidant activity of the extract correlated with its concentration (0.2~2 mg/ml) in the reaction mixtures containing linoleic acid. Upto 67% of lipid peroxidation was inhibited by 2 mg/ml of the lichen extract. The extract showed strong free radical scavenging activity similar to that of BHA (positive control) in a manner of concentration dependent. The lichen extract also showed moderate effects on superoxide anoin scavenging activity and reducing power, which was not so effective as that of Quercetin and BHA used as positive controls. This study suggests that T. vermicularis lichen can be used as a novel source of natural antioxidant.
Butylated Hydroxyanisole ; Lichens* ; Linoleic Acid ; Lipid Peroxidation ; Methanol ; Quercetin ; Superoxides