Development of 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters as selective inhibitors of mitochondrial malate dehydrogenase (mMDH)

Eur J Med Chem. 2010 Jan;45(1):335-42. doi: 10.1016/j.ejmech.2009.10.018. Epub 2009 Oct 14.

Abstract

A collection of paullones was tested for inhibitory activity against mitochondrial malate dehydrogenase (mMDH) as a biological target for antiproliferative activity. Based on the results of this screening, 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters were developed as selective mMDH inhibitors. The new derivatives did not show noteworthy antiproliferative activity when tested on a panel of cancer cell lines, suggesting that mMDH inhibition is of minor relevance for the growth inhibition caused by paullones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzazepines / chemical synthesis*
  • Benzazepines / chemistry
  • Benzazepines / pharmacology*
  • Carboxylic Acids / chemistry*
  • Cell Line, Tumor
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Malate Dehydrogenase / antagonists & inhibitors*
  • Mitochondria / enzymology*
  • Substrate Specificity

Substances

  • Benzazepines
  • Carboxylic Acids
  • Enzyme Inhibitors
  • paullone
  • Malate Dehydrogenase