USR CNRS-Pierre Fabre No. 3388 ETaC, Centre de Recherche et Développement Pierre Fabre, 3 Avenue Hubert Curien, 31035 Toulouse Cedex 01, France.
Bioorg Med Chem. 2012 Jan 15;20(2):819-31. doi: 10.1016/j.bmc.2011.11.066. Epub 2011 Dec 8.
The interesting pharmacological properties of neoboutomellerones 1 and 2 were the basis for the assembly of a small library of analogues consisting of natural products isolated from the plant Neoboutonia melleri and of semisynthetic derivatives. As the two enone systems (C23-C24a and C1-C3) and the two hydroxyls groups (C22 and C26) of neoboutomellerones are required for activity, modifications were focused on these functional groups. Biological evaluation by using a cellular assay for proteasome activity provided clues regarding the mechanism of action of these natural products and synthetic derivatives. Certain neoboutomellerone derivatives inhibited the proliferation of human WM-266-4 melanoma tumor cells at submicromolar concentration and warrant evaluation as anticancer agents.
neoboutomellerones 1 和 2 的有趣的药理学性质是从小型文库的装配基础，包括从植物 Neoboutonia melleri 中分离出来的天然产物和半合成衍生物。由于 neoboutomellerones 的两个烯酮系统（C23-C24a 和 C1-C3）和两个羟基基团（C22 和 C26）对活性是必需的，因此修饰集中在这些功能基团上。通过使用细胞蛋白酶体活性测定法进行生物学评估，为这些天然产物和合成衍生物的作用机制提供了线索。某些 neoboutomellerone 衍生物以亚微摩尔浓度抑制人 WM-266-4 黑色素瘤肿瘤细胞的增殖，值得作为抗癌剂进行评估。
