Synthesis and inhibitory activity of ubiquinone-acetogenin hybrid inhibitor with bovine mitochondrial complex I

Bioorg Med Chem Lett. 2003 Jul 21;13(14):2385-8. doi: 10.1016/s0960-894x(03)00439-6.

Abstract

To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named it Q-acetogenin. Our results indicate that the gamma-lactone ring of acetogenins is completely substitutable with the ubiquinone ring. This fact is discussed in light of the inhibitory action of acetogenins.

MeSH terms

  • Acetogenins
  • Animals
  • Cattle
  • Electron Transport Complex I / antagonists & inhibitors*
  • Furans / chemical synthesis*
  • Furans / pharmacology*
  • Indicators and Reagents
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / metabolism
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / chemical synthesis*
  • Ubiquinone / pharmacology*

Substances

  • Acetogenins
  • Furans
  • Indicators and Reagents
  • Q-acetogenin
  • Ubiquinone
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I