Inhibition of Human 5-Lipoxygenase and Anti-Neoplastic Effects by 2-Amino-1,4-Benzoquinones

Title: Inhibition of Human 5-Lipoxygenase and Anti-Neoplastic Effects by 2-Amino-1,4-Benzoquinones

Volume: 2 Issue: 6

Author(s): Daniel Poeckel, Timo H.J. Niedermeyer, Hang T.L. Pham, Annett Mikolasch, Sabine Mundt, Ulrike Lindequist, Michael Lalk and Oliver Werz

Affiliation:

Keywords: Aminoquinones, antineoplastic activity, lipoxygenase, cancer

Abstract: We have recently presented the synthesis of 2-amino-1,4-benzoquinones by nuclear amination of phydroquinones 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 antiproliferative/ 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 μM). 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.

Cite this article as:

Poeckel Daniel, Niedermeyer H.J. Timo, Pham T.L. Hang, Mikolasch Annett, Mundt Sabine, Lindequist Ulrike, Lalk Michael and Werz Oliver, Inhibition of Human 5-Lipoxygenase and Anti-Neoplastic Effects by 2-Amino-1,4-Benzoquinones, Medicinal Chemistry 2006; 2 (6) . https://dx.doi.org/10.2174/1573406410602060591