Redox and Non-Redox Mechanism of In Vitro Cyclooxygenase Inhibition by Natural Quinones

0380682 - ÚEB 2013 RIV DE eng J - Journal Article
Landa, Přemysl - Kutil, Zsófia - Tremml, V. - Vuorien, A. - Malík, J. - Dvořáková, Marcela - Maršík, Petr - Kokoška, L. - Přibylová, Marie - Schuster, D. - Vaněk, Tomáš
Redox and Non-Redox Mechanism of In Vitro Cyclooxygenase Inhibition by Natural Quinones.
Planta medica. Roč. 78, č. 4 (2012), s. 326-333. ISSN 0032-0943. E-ISSN 1439-0221
R&D Projects: GA ČR GP525/09/P528; GA MŠMT ME08070
Grant - others:GA ČR(CZ) GA525/08/1179
Program: GA
Institutional research plan: CEZ:AV0Z50380511
Keywords : inflammation * prostaglandin synthase * structure-activity relationship
Subject RIV: GM - Food Processing
Impact factor: 2.348, year: 2012

In this study, ten anthra-, nine naphtho-, and five benzoquinone compounds of natural origin and five synthetic naphthoquinones were assessed, using an enzymatic in vitro assay, for their potential to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2), the key enzymes of the arachidonic acid cascade. IC50 values comparable with COX reference inhibitor indomethacin were recorded for several quinones (primin, alkannin, diospyrin, juglone, 7-methyljuglone, and shikonin). For some of the compounds, we suggest that the redox potential of quinones as the mechanisms responsible for in vitro COX inhibition because of quantitative correlation with their pro-oxidant effect. Structure-relationship activity studies revealed that the substitutions at positions 2 and 5 play the key roles in the COX inhibitory and pro-oxidant actions of naphthoquinones. In contrast, the redox mechanism alone could not explain activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional non-steroidal anti-inflammatory drugs (NSAIDs).
Permanent Link: http://hdl.handle.net/11104/0211326