期刊
PLANTA MEDICA
卷 78, 期 4, 页码 326-333出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0031-1280430
关键词
inflammation; prostaglandin synthase; structure-activity relationship; cytotoxicity; free radicals; pharmacophore modeling
资金
- Czech Science Foundation [525/09/P528, 525/08/1179]
- Austrian Science Fund NFN [S10702/S10711]
- Ministry of Education, Youth and Sports of CR [ME08070]
- University of Innsbruck
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).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据