Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer.

Abstract

Curcumin (diferuloylmethane) is a dietary phytochemical with low toxicity that exhibits growth-suppressive activity against a variety of cancer cells and possesses certain chemopreventive properties. Curcumin has already been the subject of several clinical trials for use as a treatment in human cancers. Synthetic chemical modifications of curcumin have been studied intensively in an attempt to find a molecule with similar but enhanced properties of curcumin. In this study, a series of novel curcumin analogues were synthesized and screened for anticancer activity. New analogues that exhibit growth-suppressive activity 30 times that of curcumin and other commonly used anticancer drugs were identified. Structurally, the new analogues are symmetrical 1,5-diarylpentadienone whose aromatic rings possess an alkoxy substitution at each of the positions 3 and 5. Analysis of the effects of the analogues on the expression of cancer-related genes usually affected by curcumin indicated that some induced the down-regulation of beta-catenin, Ki-ras, cyclin D1, c-Myc, and ErbB-2 at as low as one eighth the concentration at which curcumin normally has an effect. The analogues, however, exhibited neither harmful nor growth-suppressive effects on normal hepatocytes where oncogene products are not activated. They also exhibited no toxicities in vivo that they may provide effective alternative therapies for the prevention and treatment of some human cancers.

• Authors: Hisatsugu Ohori, Hiroyuki Yamakoshi, Masaki Tomizawa, Masatoshi Shibuya, Yuichi Kakudo, Atsuko Takahashi, Shin Takahashi, Satoshi Kato, Takao Suzuki, Chikashi Ishioka, Yoshiharu Iwabuchi, Hiroyuki Shibata
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 5 Issue 10 Pg. 2563-71 (Oct 2006) ISSN: 1535-7163 [Print] United States
• PMID: 17041101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one
• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Benzene Derivatives
• Ketones
• Caspase 3
• Curcumin

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis
• Benzene Derivatives
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Curcumin (analogs & derivatives, chemical synthesis, pharmacology)
• Drug Screening Assays, Antitumor
• Gene Expression Profiling
• Humans
• Ketones
• Structure-Activity Relationship