title: Simple Strategy for Taming Membrane-Disrupting Antibiotics.
abstract: A strategy has been devised for increasing the cellular selectivity of membrane-disrupting antibiotics based on the attachment of a facially amphiphilic sterol. Using Amphotericin B (AmB) as a prototype, covalent attachment of cholic acid bound to a series of α,ω-diamines has led to a dramatic reduction in hemolytic activity, a significant reduction in toxicity toward HEK293T cells, and significant retention of antifungal activity.
authors: Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors: Yuming
authors: Y
authors: Yu
authors: Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors: Mary J
authors: MJ
authors: Sabulski
authors: Department of Medicine, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors: Wiley A
authors: WA
authors: Schell
authors: Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors: Marcos M
authors: MM
authors: Pires
authors: Department of Medicine, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors: John R
authors: JR
authors: Perfect
authors: Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors: Steven L
authors: SL
authors: Regen
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002175:Candida / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D019826:Cholic Acid / Q000737:chemistry; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000666:Amphotericin B; D019826:Cholic Acid