Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB — Oak Academic Publishing
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Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB
Center for Analysis and Synthesis, Lund University, Lund, Sweden
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Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain
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Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain
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Laboratorio de Bioorganica, Instituto de Investigaciones Químicas, Universidad Mayor de San Andrés, La Paz, Bolivia
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Center for Analysis and Synthesis, Lund University, Lund, Sweden
1 Center for Analysis and Synthesis, Lund University, Lund, Sweden
2 Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain
3 Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain
4 Laboratorio de Bioorganica, Instituto de Investigaciones Químicas, Universidad Mayor de San Andrés, La Paz, Bolivia
5 Center for Analysis and Synthesis, Lund University, Lund, Sweden
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.
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