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 cinnainaldehydes have been synthesized based oil 2-hydroxycinnamaldehyde. The synthesized compounds strongly inhibited the growth of human colon tumor cells with GI(50) values of 0.6-10 mu M. Especially, 2-piperazine derivative blocked ill 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 G(2)/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 G(2)/M transition and S phase progression. (c) 2005 Elsevier Ltd. All rights reserved.