Inhibition of human 5-lipoxygenase and anti-neoplastic effects by 2-amino-1,4-benzoquinones

Med Chem. 2006 Nov;2(6):591-5. doi: 10.2174/1573406410602060591.

Abstract

We have recently presented the synthesis of 2-amino-1,4-benzoquinones by nuclear amination of p-hydroquinones with primary aromatic amines using fungal laccases as catalysts. In the present report, a series of selected 2-amino-1,4-benzoquinones was tested for biological activities, such as inhibition of human 5-lipoxygenase and anti-proliferative/anti-neoplastic effects. Compound 9 (2-[4'-(iso-propylphenyl)-amino]-5,6-dimethyl-1,4-benzoquinone) was identified as the most potent aminoquinone derivative, suppressing 5-lipoxygenase in intact human polymorphonuclear leukocytes as well as in crude enzyme preparations in the low micromolar range (IC50 = 6 microM). Structure-activity relationships are discussed. Of interest, the 5-lipoxygenase inhibitory properties of 2-amino-1,4-benzoquinones in intact cells correlated to the anti-neoplastic activities of the compounds in breast and urinary bladder cancer cell lines. Based on these features, bioactive 2-amino-1,4-benzoquinones may possess potential for the pharmacological treatment of diseases associated with elevated 5-lipoxygenase activity, in particular certain types of cancer.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Cell-Free System
  • Drug Screening Assays, Antitumor
  • Humans
  • Lipoxygenase Inhibitors*
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Lipoxygenase Inhibitors