Taming Amphotericin B.
A strategy is introduced for enhancing the cellular selectivity of Amphotericin B (AmB) and other classes of membrane-disrupting agents. This strategy involves attaching the agent to a molecular umbrella to minimize the disruptive power of aggregated forms. Based on this approach, AmB has been coupled to a molecular umbrella derived from one spermidine and two cholic acid molecules and found to have antifungal activities approaching that of the native drug. However, in sharp contrast to AmB, the hemolytic activity and the cytotoxcity of this conjugate toward HEK293 T cells have been dramatically reduced.
Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Vaclav
V
Janout
Department of Medicine, Duke University Medical Center , Durham, North Carolina 27710, United States.
Wiley A
WA
Schell
Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Damien
D
Thévenin
Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Yuming
Y
Yu
Department of Medicine, Duke University Medical Center , Durham, North Carolina 27710, United States.
John R
JR
Perfect
Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
Steven L
SL
Regen
D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D019826:Cholic Acid / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D057809:HEK293 Cells / Q000187:drug effects; D053878:Hemolytic Agents / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D013095:Spermidine / Q000737:chemistry; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D053878:Hemolytic Agents; D000666:Amphotericin B; D019826:Cholic Acid; D013095:Spermidine