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.
