Function of the Alkyl Side Chains of Deltalac-acetogenins in the Inhibitory Effect on Mitochondrial Complex I (NADH-ubiquinone Oxidoreductase)

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3555-8. doi: 10.1016/j.bmcl.2006.03.082. Epub 2006 Apr 18.

Abstract

We synthesized a series of Deltalac-acetogenins in which the two alkyl side chains were systematically modified, and examined their inhibitory effect on bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase). The results revealed that the physicochemical properties of the side chains, such as the balance of hydrophobicity and the width (or bulkiness) of the chains, are important structural factors for a potent inhibitory effect of amphiphilic Deltalac-acetogenins. This is probably because such properties decide the precise location of the hydrophilic bis-THF ring moiety in the enzyme embedded in the inner mitochondrial membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetogenins
  • Animals
  • Cattle
  • Chemical Phenomena
  • Chemistry, Physical
  • Electron Transport Complex I / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fatty Alcohols / chemical synthesis
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology*
  • Heart / drug effects
  • Hydrophobic and Hydrophilic Interactions
  • Lactones / chemical synthesis
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / enzymology
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Acetogenins
  • Enzyme Inhibitors
  • Fatty Alcohols
  • Lactones
  • Electron Transport Complex I