New and known symmetrical curcumin derivatives inhibit the formation of Fos-Jun-DNA complex

Cancer Lett. 2002 Oct 8;184(1):89-96. doi: 10.1016/s0304-3835(02)00170-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Curcumin / analogs & derivatives
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Dimerization
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Proto-Oncogene Proteins c-fos / drug effects*
  • Proto-Oncogene Proteins c-jun / drug effects*
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factor AP-1 / drug effects*
  • Transcription, Genetic
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Curcumin