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At least 19 recordsLinked to original sources
PubMed1977

Semisynthetic cephalosporins. Synthesis and structure-activity relationships of analogues with 7-acyl groups derived from 2-(cyanomethylthio)acetic acid or 2-[(2,2,2-trifluoroethyl)thio]acetic acid and their sulfoxides and sulfones.

The synthesis and in vitro and in vivo activities of a series of cephalosporins having side chains derived from 2-[(2,2,2-trifluoroethyl)thio]acetic acid or 2-(cyanomethylthio)acetic acid and with acetoxymethyl or 3-heterocyclic thiomethyl substituents at the 3 position are described. In both series, increasing the oxidation state of the side-chain sulfur atom from sulfide to sulfoxide/sulfone decreased the in vitro gram-positive activity, but the effect on gram-negative activity was variable and less pronounced. The protective effectiveness in mice infected with Escherichia coli increased as the oxidation level of the side-chain sulfur was raised from sulfied to sulfoxide/sulfone. Replacement of the 3-acetoxymethyl by a 3-heterocyclic thiomethyl group resulted in overall improvement of activity both in vitro and in vivo for all oxidation states.

Acetates↗
PubMed1979

In vivo binding of 2,3,6,2',3',6'-hexachlorobiphenyl and 2,4,5,2',4',5'-hexachlorobiphenyl to mouse liver macromolecules.

The role of metabolic activation in the binding of polychlorinated biphenyls (PCBs) to cellular macromolecules was investigated in vivo by comparing the relative binding of 2,4,5,2',4',5'-[U-14C]hexachlorobiphenyl (2,4,5), a slowly metabolized PCB, with that of 2,3,6,2',3',6'[U-14C]hexachlorobiphenyl (2,3,6), a rapidly metabolized PCB, and the appropriate controls. Each hexachlorobiphenyl was administered to mice, orally for 5 days (7.28 mg/kg/day). Following the dosing schedule, animals were killed at 1, 5 and 8 days. The concentration of each PCB was determined in liver, muscle and kidney and in purified macromolecules isolated from those tissues. The concentration of 2,4,5 was consistently higher than the concentration of 2,3,6 in all tissues studied. However, the amount of 2,3,6 bound to the purified macromolecules was consistently at least one order of magnitude greater than that of 2,4,5. The greatest binding was observed in RNA followed by protein and DNA, respectively. The purity of the macromolecules and the presence of PCB-derived radioactivity at the monomer level were confirmed. This is the first report of 14C-labeled PCB being bound to purified RNA, DNA, and proteins isolated from the tissues of animals treated in vivo. The binding is thought to be covalent and to be the result of metabolic activation.

Animals↗
PubMed1977

2,3-Dihydro-9H-isoxazolo[3,2-b]quinazolin-9-ones and 3,4-dihydro-(1,2)-oxazino [3,2-b]quinazolin-10(2H)-ones.

Two series of compounds, 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-ones and 3,4-dihydro-(1,2)-oxazino-[3,2-b]quinazolin-10(2H)-ones, were synthesized and evaluated for anti-inflammatory, antipyretic and analgesic activity. The isoxazolo compounds were generally more active than their oxazino homologs. Three compounds, i.e., 2,3-dihydro-9H-isoxazolo [3,2-b]quinazolin-9-one (W-2429) and its 2- and 3-methyl congeners, were the most active of all compounds tested in this study. On the basis of the biological results herein reported, W-2429 is considerably more effective than acetylsalicylic acid in inhibiting carrageenan-induced edema and in reducing brewer's yeast-induced fever in rats. Also, it was found to be more potent than propoxyphene hydrochloride in the Randall-Selitto test for analgesic activity.

Animals↗
PubMed1978

Reversible conversion from Ca(2)+-ATPase activity to Mg(2)+- and Mn(2)+-ATPase activities of coupling factor purified from acetone powder of Rhodospirillum rubrum chromatophores.

It is known that the coupling factor purified from the acetone powder of chromatophores from Rhodospirillum rubrum shows ATPase activity in the presence of Ca(2)+, but not in the presence of Mg(2)+ or Mn(2)+. The present study deals with conditions, under which the Ca(2)+-ATPase activity is reversibly converted into Mg(2)+- and Mn(2)+-ATPase activites with the purified coupling factor. 1. Of the pH indicators tested, 6 kinds coverted the Ca(2)+-ATPase activity into Mg(2)+- and Mn(2)+-ATPase activities in the order, ethyl orange greater than tropaeolin 000 greater than or equal to metanil yellow greater than tropaeolin 00 greater than ethyl red greater than or equal to bromthymol blue. 2. Of the detergents tested, those other than Triton X-100 and Brij 58 caused the conversion described above; dodecylsulfonate was most effective, whereas dodecylpyridinium chloride was moderately effective. 3. 2,4-Dinitrophenol stimulated approximately two-fold the Ca(2)+-ATPase activity, but not the Mg(2)+- or Mn(2)+-ATPase activity at all. However, in the presence of dodecylpyridinium chloride, the pH indicator remarkably stimulated the Mg(2)+- and Mn(2)+-ATPase activities, accompanied with a partial inhibition of the Ca(2)+-ATPase activity. Methyl red and ethyl red showed similar effects. 4. All the nucleoside triphosphates tested can serve as the substrate. ATP was most effective for the Ca(2)+-ATPase activity, whereas dATP was most effective for the Mg(2)+- and Mn(2)+-ATPase activities induced by ethyl orange. 5. In the presence of ethyl orange, the ATPase activity was induced by various divalent cations in the following order of effectiveness, Mg(2)+ greater than Zn(2)+ greater than CO(2)+ greater than Mn(2)+ greater than Ni(2)+. 6. The mechanism of the reversible conversion from the Ca(2)+-ATPase activity to the Mg(2)+- and Mn(2)+-ATPase activities by pH indicators and detergents is discussed.

Bacterial Chromatophores↗
PubMed1977

Preparation of (S)2-methylsuccinate and (2S,3S) [2,3-2H]2-methylsuccinate by biohydrogenation of 2-methylfumarate.

2-Methylfumarate can be hydrogenated by resting cells of Proteus mirabilis under an atmosphere of hydrogen gas. Optically pure (S)2-methylsuccinate is formed in a yield greater than 95%. The hydrogen addition, presumably catalyzed by the fumarate reductase, occurs in a trans fashion, as with succinate dehydrogenase of mammalian systems. Only one reactive enzyme-substrate complex with 2-methylfumarate seems to be possible.

Fumarates↗
PubMed1979

[Derivatives of 2,3,4,5,-tetrahydro-1H-pyrido-(3,2-b)azepine and 2,3,4,5-tetrahydro-1H-pyrido(2,3-b)azepine and their corresponding lactams. II. Synthesis and pharmacologic study of their psychotropic activity].

Preparation of the N-(2-diethylaminoethyl) derivatives of lactam (II) and of the N-(3-dimethylaminopropyl) derivative of lactam (XI) is described. Synthesis of the N-[4-(2-hydroxyethyl)piperazinylacetyl]- and 1-carbothiamide derivatives of azepine (I) and of the n-(chloroformyl)- and N-(carbamoyl) derivatives of azepine (XII) are also described. Some pharmacological results indicate a partial tranquilizing activity.

Animals↗
PubMed1979

Metabolic and mutagenicity studies on DDT and 15 derivatives. Detection of 1,1-bis(p-chlorophenyl)-2,2-dichloroethane and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (kelthane acetate) as mutagens in Salmonella typhimurium and of 1,1-bis(p-chlorophenyl) ethylene oxide, a likely metabolite, as an alkylating agent.

Using a novel in vitro technique, whereby microsomal enzymes were embedded in an agar layer to prolong their viability, 1,1-bis(p-chlorophenyl) ethylene(DDNU), a mammalian metabolite of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), was converted by microsomal mono-oxygenases of mouse liver into 1,1-bis(p-chlorophenyl)-1,2-ethanediol (DDNU-diol). The putative epoxide intermediate, 1,1-bis(p-chlorophenyl)ethylene oxide (DDNU-oxide), a new compound, was synthesized; it showed weak alkylating activity with 4-(4-nitrobenzyl)pyridine but was not mutagenic in Salmonella typhimurium strains TA100 and TA98. DDT and 13 of its metabolites or putative synthetic derivatives, including 1,1-bis(p-chlorophenyl)-2,2-dichloroethylene (DDE), 1 1,1-bis(p-chlorophenyl)-2-chloroethylene (DDMU), 1,1-bis(p-chlorophenyl)-2-chloroethane (DDMS)-DDNU, 2,2-bis(p-chlorophenyl)ethanol (DDOH), bis(p-chlorophenyl)acetic acid (DDA) and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethanol (Kethane), caused no mutagenic effects in S. typhimurium strains TA100 or TA98, either in the presence or absence of a mouse-liver microsomal fraction. 1,1-Bis(p-chlorophenyl)-2,2,2-trichloroethyl acetate (Kelthane acetate) was a direct-acting mutagen in strain TA100, whereas 1,1-bis(p-chlorophenyl)-2,2-dichloroethane (DDD) was mutagenic in TA98, only in the presence of a mouse-liver microsomal system. The results are discussed in relation to possible pathways whereby DDT is activated to mutagenic and/or carcinogenic metabolites.

Alkylation↗
PubMedDate not supplied

[Identification of beta, beta-caroten-2-ol and beta, beta-carotene-2,2'-diol in the stick insect, Carausius morosus Br.; a reinvestigation study].

Two major carotenoids of the stick insect were reinvestigated and shown to be beta,beta-caroten-2-ol and beta,beta-carotene-2,2'-diol and not isocryptoxanthin (beta,beta-carotin-4-ol) and isozeaxaanthin (beta,beta-carotene-4,4'-diol). Both pigments are esterified with fatty acids. The identification is based on cochromatography with authentic 2-, 3- and 4-isomers of the mono- and dihydroxy pigment, mass spectra, and chemical behaviour. In acid solution beta-beta-carotene-2,2'-diol is specifically dehydrogenated and rearranged to ketones with retro structures in analogy to the reactionof beta,beta-caroten-2-ol as recently reported. The final product of the diol is 4,5-dihydro-4,5'-retro-beta,beta-carotene-2,2'-dione. This is the first demonstration of beta,beta-carotene-2,2'-diol in an animal.

Animals↗
PubMed1979

Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose (2-DG): differential effect of 2-DG on effector cells isolated early or late after alloantigenic stimulation in vitro.

The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on the functional activity of various populations of cytolytic T lymphocytes (CTL) has been compared. Under aerobic conditions, CTL harvested at the peak of the response (day 4) in primary or secondary mixed leukocyte cultures (MLC) were much more readily inhibited by 2-DG that CTL obtained from MLC at later times (day 11 to 18) or from the peritoneal cavity of alloimmune mice. Quantitatively, 0.4 mM 2-DG was sufficpient to inhibit cytolysis by 50% in day 4 CTL populatons, whereas 25 mM had little or no effect on day 11 to 18 CTL. Evidence was obtained that inhibition of cytolysis by 2-DG under these conditions was accompanied by a parallel inhibition of effector:target cell binding. In contradistinction to these findings, the cytolytic activity of both day 4 and day 11 MLC cells was readily inhibited by 2-DG under conditions where cell respiration was blocked by sodium azide. Furthermore, uptake of radiolabeled 2-DG was observed under aerobic conditions in both day 4 and day 11 MLC cells. These results strongly suggest that inhibition of cytolysis by 2-DG under aerobic conditions is mediated via a direct effect on CTL which is independent of the consequences of energy depletion. An indirect method by which CTL may be inhibited by 2-DG is suggested.

Animals↗
PubMed1975

Hydrolysis of nucleoside phosphates: IV. The metal ion-nucleic base interaction in the Cu2+-promoted dephosphorylation of the 5'-di- and 5'-triphosphates of cytidine, inosine and guanosine, and their protection toward hydrolysis by coordination to Cu(2,2'-bipyridyl)2+.

The dephosphorylation of CTP, GTP, ITP, ATP, CDP, GDP, IDP and ADP was characterized by measuring the first-order rate constant (50 degrees; I = 0.1, NaClO4) in dependence on pH (2 to 10). Except with CTP and CDP, the reactions are significantly accelerated by Cu2+ and pass through pH optima. By computing the pH dependence of the distribution of the several species present in the nucleotide (NP) systems, it is shown that the most reactive species is Cu(NP). Cu(NP-H), where N(1) is deprotonated, is somewhat less reactive. In both types of complexes, a metal ion-nucleic base interaction, which is responsible for the increased reactivity, occurs, i.e., macrochelates involving the phosphate chains and the base moieties are formed. In accord herewith, CTP and CDP are rather stable as the coordination tendency of the cytosine moiety is small. Furthermore, in the ternary complexes Cu(2,2'-bipyridyl)(NP) and Cu-(2,2'-bipyridyl)(NP-H), where the formation of a macrochelate is inhibited, the nucleotides are protected. The structure-reactivity relationship is also evident with Cu(ITP)2- and Cu(IDP)- which exist only in part as macrochelates; hence, they are less reactive than for example Cu(ATP)2- or Cu(ADP)-. With the aid of the initial rate, vo = d[PO4(3-)]/dt, the rate laws of the ascending side of the pH optima were determined: vo = k[Cu(NP)]/[H+]. A reaction mechanism that includes an intermolecular attack of OH- at the terminal phosphate group is proposed. The descending side of the pH optimum is attributed to the formation of CU(NP)(OH) or Cu(NP-H)(OH), where the Cu2+-base interaction is insignificant. However, these hydroxy complexes are still somewhat faster dephosphorylated than the free nucleotides. This is attributed to an intramolecular attack of the bound OH- at the terminal phosphate group.

2,2'-Dipyridyl↗
PubMed1978

Transfer of 2,4,5,2',4',5'-hexachlorobiphenyl and 2,2-bis-(p-chlorophenyl),1,1,1-trichloroethane (p,p'-DDT) from maternal to newborn and suckling rats.

Pregnant rats were given a small dose of 14C-2,4,5,2',4',5'-hexachlorobiphenyl (HCB) and 3H-DDT intraperitoneally. The transfer of HCB and DDT through the placenta and milk was then investigated. Transfer through the placenta was 2.7 and 1.5% (respectively) of the initial doses; transfer through milk was 39.2 and 21.5%. HCB is obviously more transferable than DDT through the placenta and milk, the ratio of the amount of HCB transferred through milk to the amount transferred through the placenta agrees with that for DDT. Concentrations of HCB and DDT in the whole suckling rat increases rapidly and is similar to the sigmoidal growth curve and change in lipid concentration. Therefore, the concentrations of the chemicals in the maternal tissue generally decrease in comparison with those of nonpregnant rats.

Animal Population Groups↗
PubMed1979

Absolute configuration of glycerol derivatives. 7. Enantiomers of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane (WB-4101), a potent competitive alpha-adrenergic antagonist.

The enantiomers of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane (4) were prepared from the chiral 2-[(tosyloxy)methyl]-1,4-benzodioxanes [(2S)- and (2R)-5]. The corresponding (2R)- and (2S)-2-(aminoethyl)-1,4-benzodioxanes [2R)- and (2S)-7] were prepared by a modified Gabriel synthesis and converted to the enantiomers of 4 by condensation with 2,6-dimethoxyphenoxyacetaldehyde (8) and reduction of the intermediate imine with NaBH4. The enantiomer (2S)-4 was 40--50 times as potent as the enantiomer (2R)-4 in antagonizing the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips, showing a pA2 = 9.0. This result is consistent with the previous observation that S enantiomers of 2-[(alkylamino)methyl]benzodioxanes are more potent antagonists at a alpha-adrenergic receptors than the R enantiomers.

Adrenergic alpha-Antagonists↗
PubMed1978

Effects of pure chlorobiphenyls (2,4',5-trichlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl) on the post-natal growth in mice.

The post-natal growth rate of young mice, pre- and post-natally exposed to either 2,4',5-trichlorobiphenyl or 2,2',4,4',5,5',-hexachlorobiphenyl has been studied. The results show that both the chlorobiphenyls have the ability toincrease the post-natal growth rate in mice and they indicate that this ability of 2,4',5-trichlorobiphenyl is most pronounced in females whereas that of 2,2',4,4',5,5',-hexachlorobiphenyl is most pronounced in males.

Age Factors↗
PubMed1978

Effects of pure chlorobiphenyls (2,4',5-trichlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl) on the reproductive capacity in female mice.

The effects of two pure chlorobiphenyls (2,4',5-trichlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl) on the reproductive capacity in female mice have been studied. The results obtained show that females given 0.5 mg 2,5',5-trichlorobiphenyl (TCB)/day or 0.5 mg 2,2',4,4',5,5'-hexachlorobiphenyl (HCB)/day for six consecutive days, starting on the first day of pregnancy, have significantly lower frequencies of implanted ova than the control females, whereas the frequency of implanted ova does not differ either between females given 0.05 mg/day of TCB or HCB and the control females, or between females given TCT 0.05 mg/day or 0.5 mg/day and those given the corresponding dose of HCB. Females given 0.5 mg/day of TCB or HCB, respectively, also have significantly higher contents in the livers of cytochrome P-450, on Day four of pregnancy, than the control females. The results also show that, under the experimental conditions used, neither the frequency of pregnancies nor the number of implanted ova per pregnant female differ significantly between the different groups.

Animals↗
PubMed1979

[Determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 2,4,5-trichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid-alkylesters and in the corresponding herbicide formulations (author's transl)].

A method is described for the determination of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T), 2,4,5-T-Akylesters and commercial herbicide formulations containing these substances. TCDD is extracted from alkaline solution with n-hexane and purified by column chromatography on silica gel and Florisil. TCDD is determined by gas-liquid chromatography with EC-detection. For TCDD-additions of 20 micron/kg to herbicide formulations recoveries of dioxin are 96--104%. The detection limit is about 5 microgram/kg 2,4,5-T.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1977

Effects of pure chlorobiphenyls (2,4',5-trichlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl) on the disappearance of 14C from the blood plasma after intravenous injection of 4-14C-progesterone and on the hepatic drug metabolizing system in the female rat.

Effects of two pure chlorobiphenyls (2,4',5-trichlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl) on the hepatic drug metabolizing system and on the elimination rate of 14C from the blood after intravenous injection of 4(-14)C- progesterone have been studied in the female rat. The results obtained show that females pre-treated with small amounts of 2,2',4,4'5,5'-hexachlorobiphenyl (o.5 mg/day for 14 consecutive days) have significantly higher elimination rates of 14C (originating from intravenous injection of 4(-14C-progesterone) from the blood plasma, significantly higher content of hepatic cytochrome P-450 and significantly heavier livers than control females. On the other hand, trichlorobiphenyl (0.5 mg/day for 14 consecutive days) do not differ significantly from the results obtained from control females.

Administration, Oral↗
PubMed1978

A new cephalosporin. SCE-963: 7-[2-(2-aminothiazol-4-yl)-acetamido]-3-[[[1-(2-dimethylaminoethyl)-1h-tetrazol-5-yl]-thio]methyl]ceph-3-em-4-carboxylic acid. Chemistry and structure-activity relationships.

The synthesis and the in vitro and in vivo antimicrobial activities of a series of 7-[2-(2-aminothiazol-4-yl)acetamido]cephalosporins (1) having varied 3-substituents, such as methyl, hydroxymethyl, acetoxymethyl, pyridiniomethyl and heterocyclicthiomethyls, are described. The derivatives having five membered heterocyclicthiomethyls exhibited strong inhibitory activities against Gram-negative organisms including some strains of Escherichia coli and Proteus morganii which are insensitive to cefazolin and cephaloridine. Pronounced activities were noted with 7-[2-(2-aminothiazol-4-yl)-acetamido]-3-[[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thio]methyl]ceph-3-em-4-carboxylic acid (1y; SCE-963).

Animals↗