Isoapoptolidin: structure and activity of the ring-expanded isomer of apoptolidin.
[formula: see text] Apoptolidin (1) is a novel oncolytic lead that induces apoptosis in transformed cell lines with exceptional selectivity. We report the isolation and characterization of a ring-expanded macrolide isomer of apoptolidin: isoapoptolidin (2). The solution conformation of isoapoptolidin is described. The rate of isomerization was measured under biologically relevant conditions and found to approach equilibrium within the time frame of most cell-based assays. Isoapoptolidin's ability to inhibit mitochondrial F0F1-ATPase is over 10-fold less than that of apoptolidin.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Gulledge
Aaron V
AV
Jankowski
Orion D
OD
Seto
Haruo
H
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007536:Isomerism; D007700:Kinetics; D018942:Macrolides; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D012995:Solubility; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D018942:Macrolides; D025261:Mitochondrial Proton-Translocating ATPases; C114125:apoptolidin