title: Inhibition of human 5-lipoxygenase and anti-neoplastic effects by 2-amino-1,4-benzoquinones.
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.
authors.affiliation: Department of Pharmaceutical Analytics, Institute of Pharmacy, Eberhard-Karls-University Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poeckel
authors.forename: Timo H J
authors.initials: TH
authors.lastname: Niedermeyer
authors.forename: Hang T L
authors.initials: HT
authors.lastname: Pham
authors.forename: Annett
authors.initials: A
authors.lastname: Mikolasch
authors.forename: Sabine
authors.initials: S
authors.lastname: Mundt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D002474:Cell-Free System; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016859:Lipoxygenase Inhibitors; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors