candicidin and mycoheptin

The effects of the polyene antibiotics nystatin (2 x 10(-5)-10(-4) mol/l), mycoheptin (1.3 x 10(-6)-10(-5) mol/l) and levorin (10(-8)-5 x 10(-5) mol/l) on isolated frog skeletal muscle fibres and whole sartorius muscles of the frog have been investigated. Cation conductance was measured under current clamp conditions using a double sucrose-gap technique. Cation effluxes were studied by means of flame emission photometry. All three antibiotics increased the cation conductance and efflux rates; however, differences between the polyenes were found in the steady state values of induced cation transport at a given concentration. The values of both induced conductance gA infinity and efflux rate constants KA formed the following sequence: levorin > mycoheptin > nystatin, demonstrating a correlation with the order of antifungal activities. The dose-response curves of lg polyene-induced cation transport against lg of antibiotic concentration in our experiments had slope values which were much lower than those in bilayers: 1.7 and 1.3 for nystatin and mycoheptin, respectively, whereas the aromatic heptaene levorin had an even smaller concentration dependence. The decline in the equilibrium conductance caused by nystatin- and mycoheptin removal was very fast (during the first minute tau = 0.74 and 2.39 min, respectively). In contrast, levorin-induced conductance was irreversible. It is proposed that the processes which limit the rate of channel formation are different in biological and model membranes.

Topics: Animals; Antifungal Agents; Candicidin; Cell Membrane; In Vitro Techniques; Lipid Bilayers; Muscle Fibers, Skeletal; Neural Conduction; Nystatin; Polyenes; Potassium; Rana temporaria; Rubidium; Sodium

Cation conductance and efflux induced by polyene antibiotics amphotericin B (AMB), amphotericin B methyl ester (AME), nystatin, mycoheptin, and levorin on frog isolated skeletal muscle fibers and whole sartorius muscles were investigated. Conductance was measured under current-clamp conditions using a double sucrose-gap technique. Cation efflux was studied using flame emission photometry. Some new data were obtained concerning the effects of levorin and mycoheptin on biological membranes. The power dependence of polyene-induced cation transport on antibiotic concentration in muscle membrane was lower than that in bilayers. The decline in the equilibrium conductance caused by polyene removal (except for levorin) was very fast. There was reverse temperature dependence of AMB- and nystatin-induced conductances. Both induced conductance and efflux values demonstrated a correlation with the order of antifungal activities: levorin > AMB, mycoheptin > AME > nystatin, except for AME, which was more potent on yeastlike cells. These effects were interpreted in terms of possible differences in the kinetics of channel formation in biological and model membranes and in light of the role of nonconducting antibiotic forms in biological membranes.

Topics: Amphotericin B; Animals; Antifungal Agents; Candicidin; Cations, Monovalent; Electric Conductivity; In Vitro Techniques; Kinetics; Lipid Bilayers; Lithium; Muscles; Nystatin; Polyenes; Potassium; Rana esculenta; Rubidium; Sodium; Time Factors

The component composition of reference samples of polyenic macrolide antibiotics such as nystatin, mycoheptin, amphotericin B and levorin was studied by HPLC and chromatographic mass spectrometry in comparison to the WHO standards. It was shown that the samples were close by their component composition to the analogous samples of the WHO standards.

Topics: Amphotericin B; Anti-Bacterial Agents; Candicidin; Chromatography, High Pressure Liquid; Mass Spectrometry; Molecular Weight; Nystatin; Polyenes; Reference Standards; World Health Organization

All-Union Research technological Institute of Antibiotics and Medical Enzymes, Leningrad. Institute of Epidemiology, Virology and medical parasitology, Ministry of Health of the Armenian SSR. The effect of polyenic antibiotics made in the USSR on development of E. histolytica and E. moshkovski was studied. The following antibiotics were used: levorin and its derivatives, mycoheptin, amphotericin B, amphoglucamine and nystatin. The antibiotics were compared with emetine and metronidazole. Some drugs of the imidazole group were also included into the study. On the whole 15 drugs were tested for their antiamebic activity. All the polyenic antibiotics showed a high antiamebic activity. Levorin and its derivatives were the most active. Their MICs ranged from 0.1 to 5.38 micrograms/ml. The most active of the new imidazoles was 100 times less effective than sodium levorin. The studies show that the polyenic antibiotics have an antiamebic activity and a broad antiprotozoal spectrum.

Topics: Amebicides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candicidin; Drug Resistance; Emetine; Entamoeba; Entamoeba histolytica; Imidazoles; In Vitro Techniques; Microbial Sensitivity Tests; Nystatin; Polyenes

A possibility using a common test-culture in estimation of biological activity of levorin, amphotericin B, mycoheptin and nistatin was studied. It was found that C. guillier mondii, strain 40, may be used as a common test-culture. It provided satisfactory microbial growth, clear and rather large inhibition growth zones with respect to all the drugs tested.

Topics: Amphotericin B; Antifungal Agents; Candicidin; Candida; Dose-Response Relationship, Drug; Fungi; Microbial Sensitivity Tests; Mitosporic Fungi; Nystatin; Polyenes; Saccharomyces

The kinetics of peroxide formation in the process of levorin and mycoheptin oxidation at a temperature of 57 degrees C was studied. It was shown that the peroxide compounds actively participated in the processes of levorin and mycoheptin inactivation as intermediate products of their transformation. Addition of the peroxides increased the rate of the antibiotic degradation even if there was no oxygen and subsequently decreased the periods of their storage. Conditions for the use of the iodometric method for determination of the peroxides in the poyenic compounds are discussed.

Topics: Antifungal Agents; Candicidin; Chemical Phenomena; Chemistry; Drug Stability; Drug Storage; Kinetics; Peroxides; Polyenes; Spectrum Analysis; Time Factors