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Biomedical subjects

E Borowski

Publications and source records attributed to E Borowski.

At least 127 records · Page 7Linked to original sources
PubMed1983

The antibiotic edeine. XII. Isolation and structure of edeine F.

The peptide antibiotic edeine F produced by Bacillus brevis Vm4, one of the components of edeine antibiotics complex, was isolated from a fermentation broth and was also obtained by amidination of edeine D. Edeine F is composed of amino acids: (S)-beta-phenyl-beta-alanine, (S)-isoserine, (S)-2,3-diaminopropionic acid, (2R,6S)-diamino-(7R)-hydroxyazelaic acid, glycine and a polyamine guanidylspermidine. Enzymatic degradation of antibiotic with carboxypeptidase B, dinitrophenylation of edeine and of its enzymatic degradation products and synthesis of edeine F from edeine D of known structure permitted to postulate the chemical structure for edeine F.

Anti-Bacterial Agents↗
PubMed1983

The influence of electric charge of aromatic heptaene macrolide antibiotics on their activity on biological and lipidic model membranes.

Natural aromatic heptaene macrolide antibiotics and their N-acyl and methyl ester derivatives, which differ mainly in their electric net charge, were compared for their efficiency in inducing yeast growth inhibition, red blood cell lysis, and increase in the ionic permeability of large unilamellar lipidic vesicles. Antifungal activity was found to decrease in the following order: neutral congruent to positively charged greater than negatively charged compounds. Hemolytic activity decreased in the order: neutral greater than negatively charged much greater than positively charged compounds. On lipidic model membranes, themselves either positively or negatively charged, electrostatic interaction was shown to have practically no influence on the efficiency of the differently charged antibiotics. On both biological and model systems, positively charged antibiotics consistently were found to be more active on ergosterol-containing than on cholesterol-containing membranes, and were therefore considered as potentially good candidates for specific antifungal agents.

Antifungal Agents↗
PubMed1982

Synthesis and structure-activity relationships of amides of amphotericin B.

A series of aliphatic amides of amphotericin B have been synthesized. The structure of the derivatives which were obtained has been established by mass spectrometry. Their biological properties: inhibition of growth of Saccharomyces cerevisiae and hemolytic activity have been determined. The quantitative relationships between the activity of amides of amphotericin B against S. cerevisiae and their lipophilicity can be expressed by a parabolic function, whereas that between hemolytic activity and lipophilicity--by polynominal expression of fourth degree.

Amphotericin B↗
PubMed1982

The selectivity of amino acid and peptide amidination with O-methylisourea.

Selectivity of amidination using ornithine as model amino acid was investigated in detail. The results obtained were taken advantage of for studying the reactions with other polyfunctional amino acids: beta-tyrosine, isoserine, 2,3-diaminopropionic acid, 2,6-diamino-7-hydroxyazelaic acid and with the pentapeptide amide, edeine A. It was found that, if the appropriate conditions are maintained, selective amidination of more basic amino groups of polyamino compounds is possible when these groups are bound to the primary alkyl.

Amides↗
PubMed1981

Repair of membrane alterations induced in baby hamster kidney cells by polyene macrolide antibiotics.

We studied the correlation between chemical characteristics of 13 polyene macrolide antibiotics and the ability to repair the membrane permeability changes induced by polyenes in BHK-21 cells grown in shaker culture. It had been demonstrated that large-macrolide-ring polyenes with rigid molecules (heptaenes) induced specific membrane permeability pathways which were repaired by the eucaryotic cells under the proper conditions. The influence of environmental conditions on the repair process was examined. Aureofacin trimethylammonium methyl ester derivative was used as a selected representative of polyene macrolides inducing specific pathways. The factors influencing the repair process, monitored by measuring the ability of BHK-21 cells to control K+ membrane transport, were examined during and after cell contact with the antibiotic. We found that the repair process was dependent upon the temperature, the concentration of the antibiotic, time of its contact with cells, potassium concentration in the medium, and availability of an energy source. The repair process occurred in the presence of cycloheximide, which inhibited protein synthesis in BHK-21 cells. Results showed that the repair process plays an important role in mammalian cell recovery from the toxic effects of polyenes.

Animals↗
PubMed1981

Differential selective toxicity of DMS-aureofacin components.

Trimethylammonium methyl esters (DMS) of polyene macrolides are products of the methylation of native polyene antibiotics with dimethyl sulfate. We isolated individual components of the DMS-aureofacin complex and characterized their toxicity and activity to induce permeability changes in cell membranes. The DMS-aureofacin complex contained five components readily separated by thin-layer chromatography on polygram cellulose plates. DMS-Aureofacin A, a major component of the complex (90%), showed poor selective toxicity between yeast cells and mammalian cells grown in culture. DMS-Aureofacin B (6%) and DMS-aureofacin E (4%) exhibited very high biological activities and differed qualitatively in selective toxicity. DMS-Aureofacin B was much more active for mammalian cells than for yeast cells. In contrast, DMS-aureofacin E was much more active for yeast cells than for mammalian cells. DMS-Aureofacin C and D were present in the complex in only minute quantities which did not permit their biological characterization.

Animals↗
PubMed1981

Epoxypeptide antibiotic tetaine mimics peptides in transport to bacteria.

Tetaine induced the lysis of Escherichia coli cells. Several di- and tripeptides were found to protect this cells against tetaine action. Certain peptides are able to diminish the inhibition by tetaine of diaminopimelic acid incorporation into peptidoglycan and the extent of this corresponds to the protection of the cells against the tetaine-induced lysis. The data indicate that tetaine enters E. coli cells predominantly by dipeptide permease and in part by one or more oligopeptide permease system. A number of di- and tripeptides diminished the inhibitory effect of tetaine on the incorporation of lysine into peptidoglycan of Staphylococcus aureus Oxford. In contrast to E. coli, tetaine seems to be transported into S. aureus by a single transport system.

Anti-Bacterial Agents↗
PubMed1981

Esters and amides of edeine A.

Methods for the synthesis of esters and amides of edeine A were developed and a number of derivatives of this type was obtained and characterized. The antimicrobial activities of the derivatives are comparable to the activity of the native antibiotic and indicate that the presence of free carboxyl group in edeine is not essential for its biological assay.

Anti-Bacterial Agents↗
PubMed1981

Cation permeability induced by two aromatic heptaenes, vacidin A and candicidin D on phospholipid unilamellar vesicles.

The cationic permeability induced by two aromatic heptaenes, vacidin A and candicidin D, has been studied on egg yolk L-alpha-phosphatidylcholine single walled vesicles as a function of cholesterol and ergosterol concentration. For comparison amphotericin B and nystatin were also tested. Vacidin A and candicidin D elicit cation permeability in both types of vesicles in the same concentration ranges and exhibit only quantitative differences in cholesterol and ergosterol vesicles. The active concentration range is of the same order of magnitude as the active concentration range of amphotericin B, at variance with what is obtained on biological cells. This difference is interpreted in term of mechanism of action of polyene on both biological and model membranes.

Amphotericin B↗
PubMed1980

Dissociation between the induction of potassium efflux and cytostatic activity of polyene macrolides in mammalian cells.

The paper contains data on the induction of K+ efflux and viability of baby hamster kidney (BHK-21) cells after their treatment with macrolide antibiotics inducing specific pores in membrane. New water-soluble semisynthetic derivatives of amphotericin B and aureofacin (N-glycosyl and trimethylammonium methyl ester derivatives) as well as the parent compounds were used to compare the concentration of antibiotics inducing permeabilizing and cytostatic effects. We found that a two- to eight-times-higher concentration of polyene antibiotic was required to observe a cytostatic effect than for release of 50% of the cellular potassium (K50 concentration) from BHK-21 cells. These differences were larger for water-soluble derivatives than for the parent compounds. The amount of intracellular potassium in treated cells incubated under optimal growth conditions was higher than in cells which had been further washed with K+-free maintenance medium. The membrane permeability changes induced by low concentrations of specific polyenes were observed to be reversible. BHK-21 cells were able to repair polyene-induced membrane permeability within 3 to 12 h under optimal growth conditions, after cell treatment with K50 concentration of specific macrolide antibiotics. The repair phenomenon is postulated as an explanation for the dissociation observed between permeabilizing and cytostatic effect of specific polyenes in BHK-21 cells.

Amphotericin B↗
PubMed1979

Energy dependence and reversibility of membrane alterations induced by polyene macrolide antibiotics in Chlorella vulgaris.

The requirement of metabolic energy for the interaction of polyene macrolide antibiotics with eukaryotic organisms remains a controversial subject (for review see ref. 1) It has been claimed that the lethal binding of these antibiotics to the sterol target component of the hydrophobic core of the membrane, in accordance with the model of de Kruijff and Demel, is an energy-dependent process. When energy production is reduced by removal of all metabolisable substrates or by adding metabolic inhibitors, polyene binding and antifungal effects are also reduced. Metabolic energy may be required to maintain binding site accessibility or to move antibiotic molecules to the active site. The interaction is also restricted at low temperatures, possibly because of the reduced thermal mobilities of the groups concerned with antibiotic uptake. However, it should be emphasised that the interaction of polyene macrolides with artificial lipid membranes is a purely physicochemical process, although the type of permeability pathways induced are similar to those observed in natural membranes. Using Chlorella vulgaris as a model organism, we demonstrate here that the interaction of polyene macrolides with sensitive cells and the induction of lethal membrane permeability changes are energy-dependent processes or purely physicochemical phenomena, depending on the structure of the antibiotic used.

Anti-Bacterial Agents↗
PubMed1979

Changes of adrenoceptor-mediated responses in the pithed rat during propylthiouracil-induced hypothyroidism.

Adrenoceptor-mediated responses of the cardiovascular system during propylthiouracil-induced hypothyroidism were investigated. Interfering nervous reflexes could be circumvented by using pithed rats. Cardiac beta-adrenoceptor-mediated acceleration of heart rate following electrical stimulation or injection of noradrenaline and isoprenaline was markedly diminished even after 2 weeks of treatment. This loss of beta-sensitivity prevented the study of possible changes of presynaptic regulatory adrenoceptors in this test model. Taking the increase in diastolic blood pressure after application of alpha-agonists as index of the sensitivity of vascular alpha-adrenoceptors we found these to have been desensitized in the hypothyroid state. According to these results the lack of thyroid hormones exerted a similar effect on cardiac beta- and on vascular alpha-adrenoceptors.

Animals↗