TITLE:
Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB
AUTHORS:
Rodrigo Villagomez, Juan Antonio Collado, Eduardo Muñoz, Giovanna Almanza, Olov Sterner
KEYWORDS:
Damsin, α Methylene-γ-Lactone Sesquiterpenoids, Anti-Cancer Activity
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.7 No.10,
August
14,
2014
ABSTRACT: Damsin (1) is a natural pseudoguaianolide sesquiterpene that inhibits NF-κB, a protein complex that controls the transcription of DNA in mammalian cells, and has a potential for standing model for the development of new anti-cancer lead structures. In order to do a preliminary structure-activity study and improve the anti-cancer activity, fourteen derivatives and analogs were prepared and evaluated. These were chosen to represent both structural diversity and structural novelty. The importance of α methylene-γ-lactone moiety for the anti-cancer activity was confirmed, even though other features in the scaffold were shown to be important for the activity. In some cases a new substitution negatively affected the initial activity, however, two analogues, indolo [3,2-c]-4-desoxydamsin (5) and ambrosin (6), were found to be more potent.