NF-kappaB-inhibiting naphthopyrones from the Fijian echinoderm Comanthus parvicirrus.
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.
Folmer
Florence
F
Department of Chemistry, University of Aberdeen, Old Aberdeen, UK.
Harrison
William T A
WT
Tabudravu
Jioji N
JN
Jaspars
Marcel
M
Aalbersberg
William
W
Feussner
Klaus
K
Wright
Anthony D
AD
Dicato
Mario
M
Diederich
Marc
M
D000818:Animals; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004447:Echinodermata / Q000737:chemistry*; D005367:Fiji; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C527616:6-methoxycomaparvin; C527617:6-methoxycomaparvin 5-methyl ether; D016328:NF-kappa B; D009281:Naphthalenes; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase