1. NF-kappaB-inhibiting naphthopyrones from the Fijian echinoderm Comanthus parvicirrus.
- Author
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Folmer F, Harrison WT, Tabudravu JN, Jaspars M, Aalbersberg W, Feussner K, Wright AD, Dicato M, and Diederich M
- Subjects
- Animals, Base Sequence, Crystallography, X-Ray, Fiji, Humans, I-kappa B Kinase antagonists & inhibitors, Molecular Conformation, Molecular Structure, Naphthalenes chemistry, Pyrones chemistry, Tumor Necrosis Factor-alpha pharmacology, Echinodermata chemistry, NF-kappa B antagonists & inhibitors, Naphthalenes isolation & purification, Naphthalenes pharmacology, Pyrones isolation & purification, Pyrones pharmacology
- Abstract
The two naphthopyrones 6-methoxycomaparvin (1) and 6-methoxycomaparvin 5-methyl ether (2) were isolated from a bioactive methanol-soluble extract of the Fijian echinoderm Comanthus parvicirrus. Their structures were assigned on the basis of spectroscopic methods. X-ray diffraction analysis was used to confirm the structure of 1. Both compounds were tested for their potential to inhibit the activation of the transcription factor NF-kappaB, which plays an important role in cancer development and inflammation, and the mechanism of action of the two compounds was investigated. Both naphthopyrones 1 and 2 completely inhibit TNF-alpha-induced NF-kappaB activation at a concentration of 300 microM by inhibiting the enzymatic activity of the kinase IKKbeta.
- Published
- 2008
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