Design, synthesis, and biological evaluation of air-stable nafuredin-γ analogs as complex I inhibitors

Bioorg Med Chem. 2015 Mar 1;23(5):932-43. doi: 10.1016/j.bmc.2015.01.030. Epub 2015 Jan 22.

Abstract

Nafuredin-γ (2), converted from nafuredin (1) under mild basic conditions, demonstrates potent and selective inhibitory activity against helminth complex I. However, 2 is unstable in air because the conjugated dienes are oxygen-labile. To address this, we designed and synthesized air-stable nafuredin-γ analogs. Although the complex I inhibitory activities of all the new nafuredin-γ analogs were lower than that of 2, all were in the high nM range (IC50: 300-820nM).

Keywords: Air-stable analogs; Complex I inhibitor; Nafuredin-γ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air
  • Drug Design*
  • Drug Stability
  • Electron Transport Complex I / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Pyrones / chemical synthesis
  • Pyrones / chemistry*
  • Pyrones / pharmacology*

Substances

  • Enzyme Inhibitors
  • Pyrones
  • nafuredin
  • Electron Transport Complex I