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 microM. 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.
Shin
Dae-Seop
DS
Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yoosung, Taejeon 305-600, Republic of Korea.
Kim
Jong-Han
JH
Lee
Su-Kyung
SK
Han
Dong Cho
DC
Son
Kwang-Hee
KH
Kim
Hwan-Mook
HM
Cheon
Hyae-Gyeong
HG
Kim
Kwang-Rok
KR
Sung
Nack-Do
ND
Lee
Seung Jae
SJ
Kang
Sung Kwon
SK
Kwon
Byoung-Mog
BM
D000171:Acrolein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular
D000970:Antineoplastic Agents; D000171:Acrolein; C012843:cinnamaldehyde