Institut de Science et d'Ingénierie Supramoléculaires, Université de Strasbourg, CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France.
Org Biomol Chem. 2014 Jan 14;12(2):370-5. doi: 10.1039/c3ob42049c.
A significant portion of bioactive secondary metabolites are endowed with reactive functionalities that can engage in covalent interactions with their target. Sesquiterpene lactones in particular are rich in Michael acceptors that react with cysteines. Several polycyclic scaffolds derived from total synthesis or readily available polycyclic terpenes were used as the starting point in the synthesis of a library aiming to project mildly reactive functionalities (Michael acceptors or chloroacetates) with diverse geometries. Screening of the library for inhibition of the NF-κB pathway revealed several potent inhibitors that are chemically readily accessible.
大量生物活性次级代谢产物具有反应性功能，可以与靶标发生共价相互作用。特别是倍半萜内酯含有丰富的迈克尔受体，可与半胱氨酸反应。几种来源于全合成或易得的多环萜烯的多环骨架被用作合成库的起点，旨在引入具有不同几何形状的温和反应性功能（迈克尔受体或氯乙酸酯）。该文库对 NF-κB 途径抑制的筛选发现了一些化学上易于获得的有效抑制剂。
