Natural and Semi-Synthetic Pseudoguaianolides as Inhibitors of NF-κB  

作　　者：Rodrigo Villagomez Juan Antonio Collado Eduardo Munoz Giovanna Almanza Olov Sterner 

机构地区：[1]Center for Analysis and Synthesis,Lund University,Lund,Sweden [2]Laboratorio de Bioorganica,Instituto de Investigaciones Químicas,Universidad Mayor de San Andrés,La Paz,Bolivia [3]Instituto Maimónides de Investigación Biomédica de Córdoba(IMIBIC),Departamento de Biología Celular,Fisiología e Inmunología,Universidad de Córdoba,Córdoba,Spain

出　　处：《Journal of Biomedical Science and Engineering》2014年第10期833-847,共15页生物医学工程（英文）

摘　　要：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.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.

关 键 词：Damsin α Methylene-γ-Lactone Sesquiterpenoids Anti-Cancer Activity 

分 类 号：R73[医药卫生—肿瘤]