Synthesis and biological evaluation of dimeric cinnamaldehydes as potent antitumor agents

It has been reported that 2-hydroxycinnamaldehyde and 2-benzoyl-oxycinnamaldehyde inhibited the activity of farnesyl protein transferase, angiogenesis, cell–cell adhesion, and tumor growth in vivo model. In order to improve its anti-tumor activity, dimeric cinnamaldehydes have been synthesized based on 2-hydroxycinnamaldehyde. The synthesized compounds strongly inhibited the growth of human colon tumor cells with GI50 values of 0.6–10 μM. Especially, 2-piperazine derivative blocked in vivo growth of human colon tumor xenograft in nude mice at 10 mg/kg. It was found that their anti-tumor effects induce apoptosis and cell cycle arrest at G2/M phase by the compounds. It was confirmed by detection of apoptosis markers such as activated caspase-3 and cleaved PARP, and cell cycle analysis. The dimeric compounds also inhibited Cdc25B phosphatase which is essential for preinitiating G2/M transition and S phase progression.

Dimeric cinnamaldehydes (1–21) were synthesized based on 2-hydroxycinnamaldehyde. The compounds strongly inhibited the growth of human tumor cells through the inducing apoptosis in tumor cells and in vivo growth of human colon tumor xenograft in nude mice.Figure optionsDownload as PowerPoint slide