Inhibition of in vitro leukotriene B4 biosynthesis in human neutrophil granulocytes and docking studies of natural quinones.

Quinones are compounds frequently contained in medicinal plants used for the treatment of inflammatory diseases. Therefore, the impact of plant-derived quinones on the arachidonic acid metabolic pathway is worthy of investigation. In this study, twenty-three quinone compounds of plant origin were tested in vitro for their potential to inhibit leukotriene B4 (LTB4) biosynthesis in activated human neutrophil granulocytes with 5-lipoxygenase (5-LOX) activity. The benzoquinones primin (3) and thymohydroquinone (4) (IC50 = 4.0 and 4.1 μM, respectively) showed activity comparable with the reference inhibitor zileuton (IC50 = 4.1 μM). Moderate activity was observed for the benzoquinone thymoquinone (2) (IC50 = 18.2 μM) and the naphthoquinone shikonin (1) (IC50 = 24.3 μM). The anthraquinone emodin and the naphthoquinone plumbagin (5) displayed only weak activities (IC50 > 50 μM). The binding modes of the active compounds were further evaluated in silico by molecular docking to the human 5-LOX crystal structure. T...