Synthesis and biological evaluation of dimeric cinnamaldehydes as potent antitumor agents

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 GI？？ values of 0.6？10 lM. Especially, 2-piperazine derivative blocked in vivo growth of human colon tumor xenograft in nude mice at 10 ㎎/㎏. 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.