期刊
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
卷 16, 期 7, 页码 914-924出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520615666150928114425
关键词
8-hydroxypiperidine-methyl-baicalein (BA-j); anti-cancer drug; apoptosis; CDK1 inhibitor; peroxides (H2O2)
资金
- U.S. National Institutes of Health, Cancer and AIDS Research Center (NCI) [D749677-Y]
- China Dalian Science and Technology Planning Project Fund [2008E11SF167, 2010E12SF063]
Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. Natural flavones are selective CDK1 inhibitors which can suppress the proliferation of cancer cells. However, their bioavailability is poor. To solve these problems, 6 Scutellaria flavones were isolated from hydrolyzed products of Scutellaria baicalensis and used as lead compounds, 18 Scutellaria flavones cyclane-aminol Mannich base derivatives were semi-synthesized and their biological activity as novel CDK1 inhibitors was evaluated. Results indicated that the biological activity of 8-Hydroxypiperidinemethyl-baicalein (BA-j) is the highest among these compounds. BA-j is a selective CDK1 inhibitor, and has broad-spectrum anti-proliferative activity in human cancer cells (IC50 12.3 mu M). BA-j can capture oxygen free radicals (O-center dot(2)-) and selectively increase intracellular H2O2 level in cancer cells and activated lymphocytes, thus inducing their apoptosis rather than in normal cells. These findings suggest that BA-j selectively induces apoptosis in cancer and activated lymphocyte by controlling intracellular H2O2 level, and can be developed into a novel anti-proliferative agent for the treatment of cancer, AIDS, and some immune diseases.
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