Synthesis and Biological Evaluation of Scutellaria Flavone Cyclaneaminol Mannich Base Derivatives as Novel CDK1 Inhibitors

Author(s): Lisha Ha, Yuan Qian, Shixuan Zhang, Xiulan Ju, Shiyou Sun, Hongmin Guo, Qianru Wang, Kangjian Li, Qingyu Fan, Yang Zheng, Hailiang Li

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 16 , Issue 7 , 2016

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Graphical Abstract:


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 12.3μM). BA-j can capture oxygen free radicals (.O2-) 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.

Keywords: 8-hydroxypiperidine-methyl-baicalein (BA-j), anti-cancer drug, apoptosis, CDK1 inhibitor, peroxides (H2O2).

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Article Details

Year: 2016
Published on: 27 September, 2015
Page: [914 - 924]
Pages: 11
DOI: 10.2174/1871520615666150928114425
Price: $65

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