Inhibitory effects on mitochondrial complex I of semisynthetic mono-tetrahydrofuran acetogenin derivatives

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4101-5. doi: 10.1016/j.bmcl.2003.08.045.

Abstract

Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetogenins
  • Electron Transport Complex I / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Fatty Alcohols / chemical synthesis*
  • Fatty Alcohols / pharmacology*
  • Furans / chemical synthesis
  • Furans / pharmacology
  • Kinetics
  • Lactones / chemical synthesis*
  • Lactones / pharmacology*
  • Multienzyme Complexes / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors

Substances

  • Acetogenins
  • Enzyme Inhibitors
  • Fatty Alcohols
  • Furans
  • Lactones
  • Multienzyme Complexes
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I