Facile synthetic access to and biological evaluation of the macrocyclic core of apoptolidin

Org Lett. 2003 Jun 26;5(13):2299-302. doi: 10.1021/ol0346335.

Abstract

Oxidative cleavage of the C-20/C-21 bond in apoptolidin (1) provides two fragments of similar complexity, facilitating a divide-and-diversify strategy for the determination of the structural basis for apoptolidin's biological activity, the remarkably selective induction of apoptosis in sensitive cell lines. The ability of compounds derived from this cleavage to inhibit mitochondrial F(0)F(1)-ATPase is reported. [structure: see text]

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Macrolides / chemistry*
  • Macrolides / pharmacology*
  • Methanol / chemistry
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors
  • Oxidation-Reduction

Substances

  • Enzyme Inhibitors
  • Macrolides
  • Mitochondrial Proton-Translocating ATPases
  • apoptolidin
  • Methanol