Interaction of amphotericin B and its low toxic derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester, with fungal, mammalian and bacterial cells measured by the energy transfer method
| Autor: | Edward Borowski, Joanna Szlinder-Richert, Barbara Cybulska, Jolanta Grzybowska, Jacques Bolard |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Antifungal Agents
medicine.drug_class Antibiotics Pharmaceutical Science Microbial Sensitivity Tests Cell membrane Amphotericin B Cell Line Tumor Candida albicans Drug Discovery Escherichia coli medicine Humans Potency Drug Interactions Dose-Response Relationship Drug Chemistry Biological activity Fluorescence Anti-Bacterial Agents medicine.anatomical_structure Membrane Energy Transfer Biochemistry Toxicity medicine.drug |
| Zdroj: | Il Farmaco. 59:289-296 |
| ISSN: | 0014-827X |
| DOI: | 10.1016/j.farmac.2003.12.007 |
| Popis: | Amphotericin B (AMB) derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME) retains the broad antifungal spectrum and potency of the parent antibiotic, whereas its toxicity towards mammalian cells is reduced by about two orders of magnitude. The purpose of this work was to find out whether the differences observed in the toxicity of MFAME and native AMB are due to the differential drugs affinity to fungal and mammalian cell membranes. Comparative studies on AMB and MFAME biological activity and their affinity to fungal, mammalian and bacterial cells were performed. The interaction of AMB and MFAME with cells have been studied by fluorescence method based on the energy transfer between membrane fluorescent probe (donor) and the polyenic chromophore of the antibiotic (acceptor) simultaneously present in the cell membrane. The amount of the antibiotic bound to cells was indicated by the extent of fluorescence quenching of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) or 1,6-diphenyl-1,3,5-hexatriene (DPH) by polyenic chromophore of the antibiotic. The results obtained indicate that binding extent and characteristics for both antibiotics are comparable in the three types of cells studied. Dramatically lower toxicity of MFAME as compared to AMB towards mammalian cells is not related to the antibiotic-cell affinity, but rather to different consequences of these interactions for cells, reflected in membrane permeabilization. MFAME is definitely less effective than parent AMB in the permeabilizing species formation in mammalian cell membrane. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect