Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.

Abstract

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that cyclooxygenase-1 (COX-1) plays an important role in inflammation and carcinogenesis. In order to find more selective COX-1 inhibitors a series of novel curcumin derivatives was synthesized and evaluated for their ability to inhibit this enzyme using in vitro inhibition assays for COX-1 and COX-2 by measuring PGE(2) production. All curcumin analogues showed a higher rate of COX-1 inhibition. The most potent curcumin compounds were (1E,6E)-1,7-di-(2,3,4-trimethoxyphenyl)-1,6-heptadien-3,5-dione (4) (COX-1: IC(50) = 0.06 microM, COX-2: IC(50) > 100 microM, selectivity index>1666) and (1E,6E)-methyl 4-[7-(4-methoxycarbonyl)phenyl]-3,5-dioxo-1,6-heptadienyl]benzoate (6) (COX-1: IC(50) = 0.05 microM, COX-2: IC(50) > 100 microM, selectivity index > 2000). Curcumin analogues therefore represent a novel class of highly selective COX-1 inhibitors and promising candidates for in vivo studies.

• Authors: Norbert Handler, Walter Jaeger, Helmut Puschacher, Klaus Leisser, Thomas Erker
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 55 Issue 1 Pg. 64-71 (Jan 2007) ISSN: 0009-2363 [Print] Japan
• PMID: 17202703 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase Inhibitors
• Cyclooxygenase 1
• Curcumin

Topics

• Curcumin (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Cyclooxygenase 1 (drug effects)
• Cyclooxygenase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Drug Evaluation, Preclinical
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Spectrometry, Mass, Electrospray Ionization