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B Cybulska

Publications and source records attributed to B Cybulska.

At least 19 recordsLinked to original sources
PubMed1992

Polyene macrolide antibiotics: indirect stimulation of the Na+/H+ exchanger of BALB/c B lymphoid cell line, A20.

The fluorescent pH probe, 2'-7'-bis (carboxyethyl) 5-carboxyfluorescein, was used to follow changes in internal pH (pHi) induced by aromatic polyene antibiotics in the BALB/c lymphoid cell line A20. The antibiotics studied were vacidin, which contains a free carboxylic group in the position C18 of the macrolide ring, and vacidin glycyl methyl ester and perimycin, which are without free carboxylic groups. Although all of them induced transmembrane Na+ and K+ movements, only vacidin had protonophoric activity, as previously demonstrated for red blood cells [Cybulska B et al., Biochem Pharmacol 38: 1755-1762, 1989]. However, with all three antibiotics, pHi changes were observed in A20 cells. It was demonstrated that the transmembrane H+ movements resulted to different degrees, principally in the case of perimycin and vacidin glycyl methyl ester, or partially in the case of vacidin, from the stimulation of the Na+/H+ exchanger by the induced Na+ permeability. The non-aromatic polyene antibiotic amphotericin B had a low ability to increase proton permeability.

Amiloride↗
PubMed1991

One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium.

The inducement of K+ permeability through membranes by the polyene antibiotic amphotericin B (AmB) has been analyzed as a measure of the antibiotic activity. Dose-response curves have been obtained with cholesterol- and ergosterol-containing egg yolk phosphatidylcholine large unilamellar vesicles (LUVs), human erythrocytes, and Saccharomyces cerevisiae cells. Conductance changes induced by AmB in sterol-containing planar bilayer membranes have also been studied. AmB self-association in aqueous buffer was determined by circular dichroism (CD) as a function of the antibiotic concentration. Electronic absorption and CD spectra of AmB were recorded in the presence of LUVs. For given AmB concentrations, the extent of permeability inducement is dependent on the lipid concentration. On the other hand, for cholesterol-containing LUVs or erythrocytes, a critical AmB concentration had to be reached before any permeability is observed. Independent of lipid concentration, this concentration was directly related to antibiotic self-association in the aqueous buffer. The same observation was made for erythrocytes and nystatin. The AmB absorption and CD spectra were totally different for ergosterol- and cholesterol-containing LUVs. Formation of single channels by one-sided addition of AmB could be observed only in ergosterol-containing membranes. These data lead us to propose that the permeability pathways induced by amphotericin B or nystatin, in ergosterol- and in cholesterol-containing membranes, are of different natures. In the latter case the antibiotics are only active, by single-sided addition, in the self-associated form. These findings offer important clues for the design of less toxic derivatives of AmB: they should have a low degree of self-association in water.

Absorption↗
PubMed1989

Relationship between ionophoric and haemolytic activities of perimycin A and vacidin A, two polyene macrolide antifungal antibiotics.

The ionophoric and hemolytic activities of two antifungal aromatic heptaenes: vacidin A and perimycin A, were studied on human red blood cells. Measurements of hemolysis, K+ influx and efflux, H+ movement and potential difference across the cell membrane, show that the hemolytic activity, being related to the K+ permeability induced by the polyene, is strongly dependent on the ability of this polyene to induce H+ movement. It was shown that: (1) both antibiotics have approximately the same efficiency in inducing K+ permeability, but a 100-fold difference in their hemolytic activity; (2) their hemolytic activity is related to their ability to induce H+ movement; (3) the protonophoric activity requires the existence of a free carboxyl group in the macrolide ring, as in vacidin A. The hemolytic activity is determined by the intrinsic efficiency of a K+/H+ exchange induced by this polyene. With perimycin A, which lacks the free carboxyl group, the hemolytic activity is dependent on the Cl- conductive flux which slows down the K+ flux.

Acetophenones↗
PubMed1988

Quantitative structure-activity relationships in amphotericin B derivatives.

The quantitative structure-activity relationships studies of amphotericin B and its 16 semisynthetic derivatives obtained by modification at carboxyl and amino groups have been done. The results of five biological tests were subjected to principal component analysis, a numerical method useful in the investigation of large sets of data. For some compounds, also, interaction with lipidic vesicles was investigated by spectroscopic methods. The results obtained indicate that: (i) The presence of positively charged nitrogen atom (protonable or bearing fixed charge) is indispensable for biological activity and antibiotic-sterol interaction; (ii) The lack of free carboxyl group in the molecule favours the differentiation between cholesterol and ergosterol containing cells.

Amphotericin B↗