title: Significant improvement of antifungal activity of polyene macrolides by bisalkylation of the mycosamine.
abstract: [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.
authors.affiliation: Laboratorium für Organische Chemie, ETH Hönggerberg, CH-8093 Zürich, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Paquet
authors.forename: Erick M
authors.initials: EM
authors.lastname: Carreira
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D006595:Hexosamines; D018942:Macrolides; D011090:Polyenes; D009761:Nystatin; C014692:mycosamine; D000666:Amphotericin B; D010866:Natamycin