Background: It is assumed that the unfavorable selective toxicity of an antifungal drug
Amphotericin B (AmB) can be improved upon chemical modification of the antibiotic molecule.
Objective: The aim of this study was verification of the hypothesis that introduction of bulky substituents
at the amino sugar moiety of the antibiotic may result in diminishment of mammalian in
vitro toxicity of thus prepared AmB derivatives.
Methods: Twenty-eight derivatives of AmB were obtained upon chemical modification of the
amino group of mycosamine residue. This set comprised 10 N-succinimidyl-, 4 N-benzyl-, 5 Nthioureidyl-
and 9 N-aminoacyl derivatives. Parameters characterizing biological in vitro activity
of novel compounds were determined.
Results: All the novel compounds demonstrated lower in vitro activity than AmB antifungal but
most of them exhibited negligible cytotoxicity against human erythrocytes and three mammalian
cell lines. In consequence, the selective toxicity of majority of novel antifungals, reflected by the
selective toxicity index (STI = EH50/IC50) was improved in comparison with that of AmB, especially
in the case of 5 compounds. The novel AmB derivatives with the highest STI, induced substantial
potassium efflux from Candida albicans cells at concentrations slightly lower than IC50s
but did not trigger potassium release from human erythrocytes at concentrations lower than 100
Conclusion: Some of the novel AmB derivatives can be considered promising antifungal drug