These two authors equally contribute to this paper.
Design, Synthesis and Biological Evaluation of Cinnamic Acyl Shikonin Derivatives
Article first published online: 26 NOV 2012
© 2012 John Wiley & Sons A/S
Chemical Biology & Drug Design
Volume 81, Issue 2, pages 275–283, February 2013
How to Cite
Lin, H.-Y., Chen, W., Shi, J., Kong, W.-Y., Qi, J.-L., Wang, X.-M. and Yang, Y.-H. (2013), Design, Synthesis and Biological Evaluation of Cinnamic Acyl Shikonin Derivatives. Chemical Biology & Drug Design, 81: 275–283. doi: 10.1111/cbdd.12077
- Issue published online: 10 JAN 2013
- Article first published online: 26 NOV 2012
- Accepted manuscript online: 15 OCT 2012 11:48AM EST
- Received 14 August 2012, revised 21 September 2012 and accepted for publication 4 October 2012
- cinnamic acids;
- cinnamic acyl shikonin derivatives
Inducing apoptosis is an important and promising therapeutic approach to overcome cancer. Here, we described a series of novel synthesized compounds, cinnamic acyl shikonin derivatives (1b–19b), which were synthesized starting from shikonin and cinnamic acids, which exhibit anticancer activity via inducing apoptosis in vitro. Our flow cytometry results showed that compound 8b((E)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent -3-enyl-3-(3-(trifluoromethyl) phenyl)acrylate) (IC50 = 0.69, 0.65, 1.62 μm for human SW872-s, A875 and A549 cell lines, respectively) exhibited conspicuous anticancer activities and has low cell toxicity in vitro. Therefore, we considered that compound 8b is potentially to be a candidate of anticancer agent. The proliferation inhibitory effect of compound 8b was associated with its apoptosis-inducing effect by activating caspase-3, caspase-7, caspase-9, and PARP. When the level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, and cleaved PARP are rise, apoptosis of cancer cells will be induced.