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

Daniel      Poeckel; Timo   H.J.   Niedermeyer; Hang   T.L.   Pham; Annett      Mikolasch; Sabine      Mundt; Ulrike      Lindequist; Michael      Lalk; Oliver      Werz

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.

Keywords: Aminoquinones, antineoplastic activity, lipoxygenase, cancer