New and known symmetrical curcumin derivatives inhibit the formation of Fos-Jun-DNA complex.
We previously reported that curcumin, the yellow pigment of turmeric, inhibited the formation of the Fos-Jun-DNA complex. Thus, we have synthesized 12 symmetrical curcuminoids. We used a slightly modified version of Pabon's method to search for an inhibitor more potent than curcumin. Of the synthesized curcuminoids, BJC005, CHC011, and CHC007 exhibited a remarkably high inhibitory activity. Their IC(50) values are 5.4 microM, 0.30 mM, and 0.38 mM, respectively. These IC(50) data indicated that BJC005 is nearly 90 times more effective than curcumin. The BJC005 has shown a more powerful profile than momordin, which, until now, has been reported as a potent Fos-Jun inhibitor. Also BJC005 and CHC007 have not been synthesized before. We report for the first time that the novel BJC005 and CHC007 exhibit highly inhibitory activity against transcription activity.
Hahm
Eun-Ryeong
ER
Division of Chemistry and Molecular Engineering, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, South Korea.
Cheon
Gyo
G
Lee
Juhyung
J
Kim
Bonjoong
B
Park
Chihoon
C
Yang
Chul-Hak
CH
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects*; D012045:Regulatory Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000187:drug effects*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D003474:Curcumin