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.
Paquet
Valérie
V
Laboratorium für Organische Chemie, ETH Zürich, HCI H335, 8093 Zürich, Switzerland.
Volmer
Astrid A
AA
Carreira
Erick M
EM
D000666:Amphotericin B / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002175:Candida / Q000187:drug effects; D002412:Cations / Q000737:chemistry; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D002412:Cations; D000666:Amphotericin B