Inhibition of In Vitro Leukotriene B-4 Biosynthesis in Human Neutrophil Granulocytes and Docking Studies of Natural Quinones

0395042 - ÚEB 2014 RIV US eng J - Journal Article
Landa, Přemysl - Kutil, Zsófia - Temml, V. - Malík, J. - Kokoška, L. - Widowitz, U. - Přibylová, Marie - Dvořáková, Marcela - Maršík, Petr - Schuster, D. - Bauer, R. - Vaněk, Tomáš
Inhibition of In Vitro Leukotriene B-4 Biosynthesis in Human Neutrophil Granulocytes and Docking Studies of Natural Quinones.
Natural Product Communications. Roč. 8, č. 1 (2013), s. 105-108. ISSN 1934-578X. E-ISSN 1555-9475
R&D Projects: GA ČR GP525/09/P528; GA MŠMT(CZ) MEB061112
Institutional research plan: CEZ:AV0Z50380511
Keywords : 5-Lipoxygenase * Anti-inflammatory activity * Dual COX/LOX inhibition
Subject RIV: GM - Food Processing
Impact factor: 0.924, year: 2013

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 B-4 (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 mu M, respectively) showed activity comparable with the reference inhibitor zileuton (IC50 = 4.1 mu M). Moderate activity was observed for the benzoquinone thymoquinone (2) (IC50 = 18.2 mu M) and the naphthoquinone shikonin (1) (IC50 = 24.3 mu M). The anthraquinone emodin and the naphthoquinone plumbagin (5) displayed only weak activities (IC50 > 50 mu M). The binding modes of the active compounds were further evaluated in silico by molecular docking to the human 5-LOX crystal structure. This process supports the biological data and suggested that, although the redox potential is responsible for the quinone's activity on multiple targets, in the case of 5-LOX the molecular structure plays a vital role in the inhibition. The obtained results suggest primin as a promising compound for the development of dual COX-2/5-LOX inhibitors.
Permanent Link: http://hdl.handle.net/11104/0223191