MFAME, N-methyl-N-D-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: relationship between self-association andeffects on red blood cells

In aqueous solutions X-methyl-N-D-fructosyl amphotericin B methyl ester (MF AME), a novel amphotericin B derivative with low animal toxicity, similar t o its parent antibiotic, exists in three forms: monomeric, soluble and inso luble aggregates in equilibrium [1]. The aim of our work was to examine the influence of medium composition on the MFAME self-association and the rela tionship between MFAME self-association and its toxicity towards red blood cells. The toxicity of MFAME in aggregated state towards red blood cells wa s tested by measuring the induction of potassium leakage and extent of haem olysis. The proportions of antibiotic species present in various aqueous me dia were determined by analysis of the UV-Vis spectra as a function of the antibiotic concentration. Numeric decomposition of the spectra allowed iden tification of four spectral species present in MFAME solutions: monomeric a nd three aggregated forms. Our results indicate that these aggregates, name d type 1, type II and type III, are different in terms of spectral properti es, as well as effectiveness towards red blood cells. Soluble aggregate typ es I and III are the active forms of MFAME towards erythrocytes. The medium composition seems to be the main factor determining which type of antibiot ic aggregate prevails in solution. (C) 2001 Elsevier Science B.V. All right s reserved.