Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo

BMC Pharmacol. 2011 May 28:11:4. doi: 10.1186/1471-2210-11-4.

Abstract

Background: Curcumin is known to possess many anti-tumor properties such as inhibition of tumor growth and induction of apotosis. However, limited bioavailability of curcumin prevents its clinical application. A synthesized curcumin analog, 1,5-diaryl-3-oxo-1,4-pentadiene such as GO-Y030, has the improved anti-tumor potential in vitro as well as in mouse model of colorectal carcinogenesis.

Results: These compounds were divided into two groups; one is the higher anti-proliferative group, in which 79.7% of 1,5-diaryl-3-oxo-1,4-pentadienes were clustered. One of the 1,5-diaryl-3-oxo-1,4-pentadiene analogs, GO-Y078 has the most enhanced growth inhibition, and its solubility was improved, compared with curcumin. GO-Y078 inhibits NF-κB transactivation, as well as expression of TP53 and DR5 more effectively than curcumin. In a mouse model, GO-Y078 presented 1.4 fold more survival elongation that was not achieved by curcumin and GO-Y030.

Conclusions: The 1,5-diaryl-3-oxo-1,4-pentadiene analogs can yield good lead compounds for cancer chemotherapy, to overcome low bioavailability of curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkadienes / chemical synthesis*
  • Alkadienes / pharmacology
  • Alkadienes / therapeutic use
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis
  • Curcumin / pharmacology
  • Curcumin / therapeutic use
  • Drug Evaluation, Preclinical
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Solubility

Substances

  • Alkadienes
  • Antineoplastic Agents
  • GO-Y078
  • Curcumin