N-methyl-N-D-fructosyl amphotericin B methyl ester [MF-AME], a novel antifungal agent of low toxicity: monomer-micelle control over selective toxicity

• Autorzy: Cybulska B. , Gadomska I. , Mazerski J. , Grzybowska J. , Borowski E. , Cheron M. , Bolard J.
• Języki publikacji: EN

Abstrakty

EN

Rational chemical modification of amphotericin B (AMB) led to the synthesis of sterically hindered AMB derivatives. The selected optimal compound, N-methyl- N-D-fructosyl amphotericin B methyl ester (MF-AME) retains the broad spectrum of antifungal activity of the parent antibiotic, and exhibits a two orders of magnitude lower toxicity in vivo and in vitro against mammalian cells. Comparative studies of MF-AME and AMB comprising the determination of the spectroscopic properties of monomeric and self-associated forms of the antibiotics, the investigation of the influence of self-association on toxicity to human red blood cells, and of the antibiotic-sterol interaction were performed. On the basis of the results obtained it can be assumed that the improvement of the selective toxicity of MF-AME could in part be a consequence of the diminished concentration of water soluble oligomers in aqueous medium, and the better ability to differentiate between cholesterol and ergosterol.

Słowa kluczowe

EN

potassium loss; antifungal activity; circular dichroism spectroscopy; chemical modification; toxicity; amphotericin B; erythrocyte; antibiotic; selective toxicity; antibiotic-sterol interaction; mammalian cell

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 1
• Opis fizyczny: p.121-131,fig.

Twórcy

autor

Cybulska B.

• Technical University of Gdansk, 80-952 Gdansk, Poland

autor

Gadomska I.

autor

Mazerski J.

autor

Grzybowska J.

autor

Borowski E.

autor

Cheron M.

autor

Bolard J.

Bibliografia

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