amphotericin-b and fungichromin

Topics: Amphotericin B; Anti-Bacterial Agents; Candicidin; Candida albicans; Erythrocytes; Filipin; Humans; Lipoproteins; Lipoproteins, HDL; Lucensomycin; Macrolides; Nystatin; Polyenes; Potassium

Control of permeation of bleomycin A2, a well-known antitumor antibiotic, in combination with various polyene macrolide antibiotics was analyzed in cultured Chinese hamster cells in vitro. Three polyene antibiotics, filipin, pentamycin, and pimaricin, were found to enhance the action of bleomycin A2 remarkably, while amphotericin B or nystatin could not. Although DNA synthesis and colony-forming activity of polyene-sensitive Chinese hamster V79 cells were synergistically inhibited by the combination of filipin and bleomycin A2, in a polyene-resistant subline (AMBR-1) derived from V79, they were only slightly affected in the presence of both drugs. The cellular uptake of [14C]bleomycin A2 by V79 was enhanced 2- to 4-fold in the presence of increasing doses of filipin or pentamycin, but not in the presence of amphotericin B. The treatment of V79 cells with filipin for 20 to 30 min was enought to block DNA synthesis almost completely when combined with 20 microgram belomycin A2 per ml. The pretreatment of the hamster cells with 6 microgram filipin per ml for 60 min continued to enhance the inhibitory action by bleomycin A2 of DNA synthesis up to 5 hr after the removal of filipin from the cultured medium.

Topics: Amphotericin B; Animals; Antifungal Agents; Bleomycin; Cell Division; Cell Line; Clone Cells; Cricetinae; Cricetulus; DNA; Drug Synergism; Filipin; Macrolides; Natamycin; Nystatin; Polyenes

The interactions of filipin III, amphotericin B, nystatin, and lagosin with sterols in aqueous suspension and in vesicles were followed by fluorescence excitation spectra and by measurement of polarized fluorescence intensities. The equilibrium constants for association of the polyene antibiotics with aqueous suspensions of cholesterol follow the order filipin III > amphotericin B > nystatin > lagosin, in agreement with the order reported for the extent of damage these antibiotics cause in natural and model membranes. Fluorescence polarization measurements show that hydrophobic forces are primarily responsible for the formation of the complexes. Filipin III undergoes a large enhancement in fluorescence polarization on binding to aqueous suspensions of cholesterol and epi-cholesterol, and to vesicles of lecithin-cholesterol, lecithin-beta-cholestanol, and lecithinergosterol. Small increases in polarization occur on interaction of filipin III with vesicles derived from lecithin and epi-cholesterol, thiocholesterol, and androstan-3beta-ol. Amphotericin B undergoes a relatively constant enhancement in fluorescence polarization on interaction with the various lecithin-sterol vesicles used and does not display the selectivity exhibited by filipin III. It is suggested that filipin III serves as a probe of lecithin-sterol interaction.

Topics: Amphotericin B; Antifungal Agents; Cholesterol; Fatty Acids, Unsaturated; Fluorescence; Kinetics; Lactones; Macrolides; Methanol; Nystatin; Polyenes; Spectrometry, Fluorescence; Spectrum Analysis

Lampen, J. Oliver (Rutgers, The State University, New Brunswick, N.J.), James W. Gill, Peter M. Arnow, and I. Magana-Plaza. Inhibition of the pleuropneumonia-like organism Mycoplasma gallisepticum by certain polyene antifungal antibiotics. J. Bacteriol. 86:945-949. 1963.-The growth of Mycoplasma gallisepticum, a sterol-requiring pleuropneumonia-like organism (PPLO), was inhibited by certain polyene antifungal antibiotics at the following concentrations: filipin, 0.5 mug/ml; amphotericin B, 3 mug/ml; and fungichromin, 10 mug/ml. The inhibition of the organism was due to fungicidal action of the polyenes rather than to decreased availability of the sterol. The PPLO rapidly bound nystatin (NY), but was relatively insensitive to this antifungal agent or to N-acetyl-candidin (NAC). Even with a comparatively small inoculum, 100 mug of NY per ml or 50 mug of NAC per ml, were required to inhibit growth. In contrast, Saccharomyces cerevisiae, growing under similar conditions, was completely inhibited by 3 mug of NY or NAC per ml. Filipin, however, was effective against both organisms, inhibiting PPLO and yeast at 0.5 mug/ml and 3 mug/ml, respectively. The relative insensitivity of PPLO to NY was not the result of protection by the sterol present in the growth medium. These organisms, incubated for 2 hr in sterol-free buffer in the presence of 20 mug of NY per ml showed little, if any, inhibition of growth when transferred to growth medium. Under the same conditions, more than 99% of a yeast suspension was killed. It is suggested that the PPLO are primarily sensitive to the disruptive action on the cell membrane which is characteristic of the smaller polyenes (34 to 37 carbon atoms).

Topics: Amphotericin B; Antifungal Agents; Culture Media; Filipin; Macrolides; Mycoplasma; Mycoplasma gallisepticum; Mycoplasma Infections; Nystatin; Pharmacology; Polyenes; Research; Saccharomyces; Saccharomyces cerevisiae; Sterols