Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues

Org Lett. 2006 Feb 16;8(4):589-92. doi: 10.1021/ol052800q.

Abstract

[structure: see text] Apoptolidin (1) exhibits potent and highly selective apoptosis inducing activity against sensitive cancer cell lines and is hypothesized to act by inhibition of mitochondrial F(0)F(1)-ATP synthase. A series of apoptolidin derivatives, including a new intermolecular Diels-Alder adduct, were analyzed for antiproliferative activity in E1A-transformed rat fibroblasts. Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Drug Screening Assays, Antitumor
  • Fibroblasts / drug effects
  • Macrolides* / chemical synthesis
  • Macrolides* / chemistry
  • Macrolides* / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Rats
  • Tumor Cells, Cultured
  • Yeasts / enzymology

Substances

  • Antineoplastic Agents
  • Macrolides
  • Proton-Translocating ATPases
  • apoptolidin