Inhibition of human 5-lipoxygenase and anti-neoplastic effects by 2-amino-1,4-benzoquinones.
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.
Poeckel
Daniel
D
Department of Pharmaceutical Analytics, Institute of Pharmacy, Eberhard-Karls-University Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany.
Niedermeyer
Timo H J
TH
Pham
Hang T L
HT
Mikolasch
Annett
A
Mundt
Sabine
S
Lindequist
Ulrike
U
Lalk
Michael
M
Werz
Oliver
O
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
D000970:Antineoplastic Agents; D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors