title: Redox and non-redox mechanism of in vitro cyclooxygenase inhibition by natural quinones.
abstract: 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 the redox potential of quinones as the mechanism responsible for in vitro COX inhibition because of the 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 the activity of primin, embelin, alkannin, and diospyrin. For these four quinones, molecular modeling suggested similar binding modes as for conventional nonsteroidal anti-inflammatory drugs (NSAIDs).
authors.affiliation: Laboratory of Plant Biotechnologies, Institute of Experimental Botany AS CR, Prague 6-Lysolaje, Czech Republic. landa@ueb.cas.cz
authors.forename: Premysl
authors.initials: P
authors.lastname: Landa
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kutil
authors.forename: Veronika
authors.initials: V
authors.lastname: Temml
authors.forename: Anna
authors.initials: A
authors.lastname: Vuorinen
authors.forename: Jan
authors.initials: J
authors.lastname: Malik
authors.forename: Marcela
authors.initials: M
authors.lastname: Dvorakova
authors.forename: Petr
authors.initials: P
authors.lastname: Marsik
authors.forename: Ladislav
authors.initials: L
authors.lastname: Kokoska
authors.forename: Marie
authors.initials: M
authors.lastname: Pribylova
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanek
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry* / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D010936:Plant Extracts; D011809:Quinones; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2