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Title: Investigations of marine and terrestrial natural products with NF-kappaB inhibitory properties
Author: Folmer, Florence
ISNI:       0000 0001 3472 0194
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2007
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NF-kB has become a major target in drug discovery.  The oceans cover 70% of our planet and form a habitat with unique environmental properties in which organisms producing chemically unique and biomedically powerful secondary metabolites thrive.  Here, the NF-kB inhibitory potential and the mechanism of action of natural products isolated from over two hundred Fijian and Scottish marine organisms and from the Fijian plant kava (Piper methysticum) are investigated.  The study reveals that 9% of crude extracts from marine organisms strongly inhibit the activation of NF-kB.  The NF-kB inhibitory potential is equally distributed throughout the tested phyla.  The kava-derivatives kavain and flavokavains A and B, as well as the isomalabaricanes stellettin A and B, two naphthopyrones, two cembranoids, the depsipeptide jasplakinolide, and the carotenoid astaxanthin isolated from Fijian marine organisms completely inhibit NF-kB activation at concentrations of less than 200 µg/mL.  The tested compounds mainly target the binding of NF-kB to DNA and processes upstream of the degradation of the cytoplasmic inhibitor of NF-kB, IkB, which, under basal conditions, prevents the activation of NF-kB by masking NF-kB’s nuclear localization site.  Altogether, the results of the present study give a first insight into NF-kB-inhibitory mechanisms triggered by marine natural products and by ethnobotanically used kava derivatives.  Together with the outcome of a still ongoing metabolomic analysis of the distribution of NF-kB inhibitors amongst Fijian marine natural products, the results of the present study will, most certainly, lead to a rapid and sustainable yield of unique and highly potent anti-cancer and anti-inflammatory substances in the near future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available