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

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

Volume: 16 Issue: 7

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

Affiliation:

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

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.

Cite this article as:

Ha Lisha, Qian Yuan, Zhang Shixuan, Ju Xiulan, Sun Shiyou, Guo Hongmin, Wang Qianru, Li Kangjian, Fan Qingyu, Zheng Yang and Li Hailiang, Synthesis and Biological Evaluation of Scutellaria Flavone Cyclaneaminol Mannich Base Derivatives as Novel CDK1 Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (7) . https://dx.doi.org/10.2174/1871520615666150928114425