Synthesis and In Vitro Biological Properties of Novel Cationic Derivatives of Amphotericin B

Novel cationic amphotericin B derivatives as highly potent antifungal agents are reported. These semi‐synthetic derivatives of amphotericin B were elaborated through a series of modifications both on the nitrogen atom of the mycosamine and on the C‐16 carboxylic acid moiety. The antifungal activity of the new conjugates was tested against Saccharomyces cerevisiae and also against nine different strains of Candida albicans and Candida glabrata, including an amphotericin resistant strain. High potency was observed in the case of polyamine derivatives bearing two 3‐aminopropyl chains on the mycosamine. The evaluation of the biological properties also included the determination of the hemolytic activity of the compounds by measuring the EH50 values. The modular approach: The introduction of an amide function at C‐16 and a polyamine moiety on the mycosamine of amphotericin B (see graphic) lead to a significant improvement in antifungal activity and reduced toxicity.