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Results for “Ethers, Cyclic”

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At least 19 recordsLinked to original sources
PubMed1978

Structure-activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners.

This study investigates the inhibition of microtubule assembly in vitro by podophyllotoxin and its derivatives, which include in part the antitumor compounds 4'-demethylepipodophyllotoxin ethylidene beta-D-glucoside (VP-16-213) and 4'-demethylepipodophyllotoxin thenylidene beta-D-glucoside (VM-26); the cyclic ethers, cyclic sulfides, and cyclic sulfones of podophyllotoxin and deoxypodophyllotoxin; epipodophyllotoxin; picropodophyllotoxin; and several 4'-demethyl compounds. The inhibitory activity of these derivatives is sensitive to the configuration and size of substituents at position 4 in ring C and to steric features of substituents at position 12 in ring D. Decreasing activity correlates with the increasing size of the substituent at position 12, as indexed by their van der Waals radii. These results suggest that rings C and D of these drugs are involved in their interaction with the podophyllotoxin-binding site in tubulin.

Animals↗
PubMed1977

Use of ethyl ethers, deuteriomethyl ethers and cyclic n-butylboronates of hydroxychlorobiphenyls in identification of metabolites of polychlorinated biphenyls.

The mass spectra and gas chromatographic properties of a number of chlorobiphenylols, chlorobiphenyldiols, chlorophenols and naphthols, as well as their methyl, deuteriomethyl and ethyl ethers and some cyclic n-butylboronates have been investigated. Metabolism experiments with 4'-chloro-4-biphenylol showed that the selective use of ethylation and methylation is most effective in both detection and structure elucidation of metabolites partly methylated by metabolic processes. The usefulness of deuteriomethylation in such studies seems to be limited. The formation of cyclic n-butylboronates provides specific information on o-dihydroxy derivatives of chlorobiphenyls.

Animals↗
PubMed2025

Enzymatic Anti-Baldwin Ring-Closure Cascade for Fused Bicyclic Ether Formation.

Pyrenulic acids are cytotoxic polyketides isolated from the ascomycete Pyrenula sp. derived from Vietnamese lichen that are characterized by complex fused cyclic core structures. Genome sequencing, in silico sequence analysis, and RT-PCR studies identified the pyrenulic acid (pya) biosynthetic gene cluster. Based on a functional analysis of the enzymes by expression of each gene in a heterologous host using Aspergillus nidulans, we discovered two cytochrome P450s PyaJ and PyaG that effect epoxidation and hydroxylation of the alkyl chain terminal, respectively, and an α/β hydrolase PyaF that constructs a 6- and 7-membered fused bicyclic diether skeleton by catalyzing successive epoxide ring-opening 6-endo and 7-endo cyclization reactions. To elucidate the detailed mechanism of pyrenulic acid formation, we obtained PyaF as a recombinant enzyme and performed an in vitro experiment, which confirmed catalysis by PyaF of the cyclization reaction. In addition, we performed alignment analysis of PyaF with α/β hydrolases with known functions, as well as an in-depth computational study. In-depth computational analyses of the cyclization reaction pathways with density functional theory quantum mechanics and detailed characterization of PyaF by Chai-1-based protein structure modeling with molecular dynamics simulations and site-specific mutagenesis predicted the active amino acid residues of this serine α/β hydrolase to be an unusual catalytic serine tetrad involving Ser170, Asn342, Asp314, and His169, with Tyr255 and His284 acting as general bases to facilitate opening of the epoxides. Our study provides insight into how regioselectivity of enzymatic anti-Baldwin epoxide ring-opening cascades for the formation of a fused cyclic ether structure is controlled.

Cyclization↗
PubMed1979

Effect of prostaglandin endoperoxide analogue on canine renal function, hemodynamics and renin release.

We studied the effect of a stable, cyclic ether analogue of prostaglandin endoperoxide (EPA) on canine renal function, hemodynamics, and renin release. Infusion of EPA into one renal artery decreased renal blood flow in a dose dependent manner. At a dose of 10(-7) g/kg/min the renal blood flow decreased from a baseline of 384 to 267 ml/min/100 g. This flow decrease was unaltered by phentolamine and saralasin, but was potentiated by prior treatment with indomethacin. Urine flow, glomerular filtration rate, sodium, and potassium excretion all decreased in a dose dependent manner; however, neigher fractional excretion of sodium nor free water clearance showed any significant change, making direct tubular effects of EPA unlikely. EPA caused a significant increase in renin release that was completely blocked by prior treatment with indomethacin. We conclude that EPA is a potent renal vasoconstrictor and that this vasoconstriction is responsible for the renal functional changes observed. Renin release is not a direct effect of EPA but probably is secondary to an endogenously generated prostaglandin. Since EPA mimics the effects of natural prostaglandin endoperoxides on smooth muscle in vitro, it is possible that prostaglandin endoperoxide-induced vasoconstriction in vivo modulates the effects of their vasodilatory products, prostaglandin E2 and I2.

Animals↗
PubMed1978

Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level.

Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.

Adrenocorticotropic Hormone↗
PubMed1976

Induction of estrous cycles in old non-cyclic rats by progesterone, ACTH, ether stress or L-dopa.

Cycling was induced in old non-cyclic, constant estrous rats by daily injections of progesterone, ACTH or L-dopa or by subjection to ether stress. Progesterone and ACTH were the most effective agents used for re-establishing estrous cycles in these rats. Most of the progesterone- and ACTH-treated rats showed regular cycles, and their ovaries had many corpora lutea; they also showed proestrous serum LH surges. Ether stress and L-dopa mostly induced irregular cycles and fewer corpora lutea in the ovaries; a smaller number of these rats showed proestrous LH surges. After treatment with each of these agents was discontinued, most of the rats returned to constant estrus or irregular cycling.

Adrenocorticotropic Hormone↗
PubMed1979

In vitro mutagenicity and cell transformation screening of phenylglycidyl ether.

Phenylglycidyl ether (1,2-epoxy-3-phenoxy propane) (PGE) was tested for genetic activity in bacterial and mammalian tests. It was active in the Salmonella/microsome mutagenicity test. Concentration-dependent mutagenicity was demonstrated in S. typhimurium strains TA1535 and TA100 with and without rat S9, but not in strains TA98, TA1537, or TA1538. These results suggest PGE, is a direct-acting mutagen causing base substitutions. Phenylglycidyl ether did not induce 6-thioguanine-resistant mutants of Chinese hamster ovary cells, with or without rat S9, and with or without serum in the medium. Dose-dependent enhancement of SA7 virus transformation of primary hamster embryo cells was observed at concentrations of 1.6 microgram/ml and higher. In addition, this compound was able to chemically transform secondary hamster embryo cells at concentrations of 6.2 micrograms/ml and higher. At a dose of 2500 mg/kg p.o., PGE was active in the host-mediated assay using C57B1/6 X C3H mice and S. typhimurium strain TA1535. This activity represented a positive response in 2 of 5 animals tested. Murine testicular DNA synthesis was not inhibited by oral administration of PGE at 500 mg/kg.

Drug Evaluation, Preclinical↗
PubMed1979

Contact sensitivity to phenylglycidyl ether.

From among 40 workers with dermatitis who did not have contact with phenylglycidyl ether but worked with epoxy resins, 5 were positive to Epidian 5 and phenylglycidyl ether. Cross reactions between these contactants were noted in 3 of the 17 guinea pigs with primary sensitization to epoxy resin or the tested diluent. For 58 persons coming into contact with phenylglycidyl ether the frequency of sensitization to the contactant was determined and the mean period between starting work and the occurrence of dermatitis was calculated.

Animals↗
PubMed1979

Synthesis of Benzo-15-crown-5 polyethers, anticoccidial ionophore analogues.

Synthesis of eight benzo-15-crown-5 derivatives I (R = H, CO2Me, CO2H, Me; R1 = H, CO2H, CO2Me, CHO, CH=CHCO2H, CH2CH2CO2H) designed as rigid cyclic analogues of the anticoccidial ionophores is described. No anticoccidial activity was observed in chickens, but moderate activity in tissue culture was found for I (R = Me, R1 = H; R = R1 = H) and dibenzo-18-crown-6.

Animals↗
PubMed1975

About some possible anti-inflammatory properties of various membrane permeant agents.

Non steroidal anti-inflammatory drugs uncouple mitochondrial oxidative phosphorylation. They are membrane permeant agents. They also inhibit nucleic acids synthesis in lymphoid cells. Three antibiotics (valinomycin, gramicidin A, alamethicin) and one cyclic polyether (dibenzo-18-crown-6) which are potent membrane permeant agents and good uncouplers are demonstrated to inhibit such a nucleic acids synthesis. This inhibition is largely dependent on the ionic composition of the incubation medium. It is suggested on the basis of some preliminary results that these drugs, which are non-acidic molecules, should be further investigated for potential anti-inflammatory properties.

Alamethicin↗
PubMed1976

Activity of liver microsomal mono-oxygenases on some epoxide-forming cyclic tricyclic drugs. I. Kinetics in vitro.

1. The mono-oxygenase activity that forms epoxides has been studied in rat liver microsomes using as substrates carbamazepine and cyclobenzaprine, tricyclic drugs which form stable epoxides in vivo and in vitro. 2. A simple gas chromatographic method has been used to determine the amount of epoxide formed and the linearity of the enzymic reaction with time and protein concentration has been demonstrated. 3. Pre-treatment with carbamazepine increases the rate of formation of carbamazepine epoxide in rat liver microsomal preparations. 4. The effect of SKF 525-A on the formation of these epoxides has been studied.

Animals↗
PubMed1978

Cyclic polyether-protonated organic amine binding: significance in enzymatic and ion transport processes.

The cyclic polyether, 18-crown-6, reacts with protonated amines in methanol to form complexes whose formation constants (log K) decrease in the order NH4+, RNH3+ greater than R2NH2+ greater than R3NH+. In the case of the organic amines, this stability order is identical to the earlier observed permeability sequence for protonated organic amines in glyceryl dioleate bilayers treated with valinomycin, nonactin, or gramicidin, and in bullfrog and rabbit gallbladder membranes. The decrease in log K values in the above series is primarily a result of decreased enthalpy change (deltaH) values, the entropy change (TdeltaS) term being essentially constant for the systems studied.

Amines↗
PubMed1978

Open chain crown-type polyethers and pyridinophane cryptands act as ionophores upon frog motor nerve and isolated rat heart cells.

Frog motor nerves and isolated heart cells from neonatal rats were incubated with solutions of open chain crown-type polyether or pyridinophane cryptand. The following alterations in membrane excitability and energy consumption were found: 1. The non-cyclic ligand stabilizes the resting potential of the frog nerve and reduces the pulsation rate of heart muscle cells. It is reversibly bound at the cell surface and does not affect the energy metabolism of the heart cells. (formula: see text) 2. The cryptand 1,12-dioxo-2,11-diaza-5,8,21,24-tetraoxa[12-8(2,11)] (2,6)-pyridinophane) ([2.2.1py]-diamide) is irreversibly bound by the tissues. It facilitates the depolarization of the nerve and shows a positively chronotropic effect upon the heart muscle cells. Single treatment of the cell cultures with 10 microgram [2.2.1py]-diamide per ml medium increased the activities of lactate dehydrogenase and of creatine kinase. When the cell cultures were treated three times at 24 h intervals with 10 microgram complexone/ml, the creatine kinase activity of the heart muscle cells decreased by about 40%. The physiological properties of the ligands are correlated with the stability of their alkali metal ion complexes and with the rate constants of complex formation. It is concluded that [2.2.1py]-diamide can act as a passive carrier for Na+ K+.

Animals↗