Significant improvement of antifungal activity of polyene macrolides by bisalkylation of the mycosamine.
[reaction: see text] New derivatives of Amphotericin B (AmB) were synthesized through a double reductive alkylation of the mycosamine. These derivatives of AmB displayed superior antifungal activity against Saccharomyces cerevisiae wild-type strain and especially in the case of an AmB-resistant Candida albicans strain. Moreover, these compounds are potential drug candidates because of significantly reduced hemotoxicity compared to AmB. Furthermore, the same mycosamine modification can be applied to other polyene macrolides such as Nystatin and Pimaricin to improve their antifungal activity.
Paquet
Valérie
V
Laboratorium für Organische Chemie, ETH Hönggerberg, CH-8093 Zürich, Switzerland.
Carreira
Erick M
EM
D000478:Alkylation; D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D004352:Drug Resistance, Microbial; D006595:Hexosamines / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010866:Natamycin / Q000737:chemistry / Q000494:pharmacology; D009761:Nystatin / Q000737:chemistry / Q000494:pharmacology; D011090:Polyenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
D000935:Antifungal Agents; D006595:Hexosamines; D018942:Macrolides; D011090:Polyenes; D009761:Nystatin; C014692:mycosamine; D000666:Amphotericin B; D010866:Natamycin