Wiemann Jana, Heller Lucie, Csuk René
Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Eur J Med Chem. 2018 Apr 25;150:176-194. doi: 10.1016/j.ejmech.2018.02.060. Epub 2018 Feb 21.
The promising combination of natural product leads and their derivatization by isocyanide-based multicomponent reactions (IMCRs) has gained interest in accessing diversity-oriented libraries with auspicious pharmacological potential. Therefore, a set of 34 Ugi and 3 Passerini products was successfully synthesized starting from naturally occurring triterpenoids, i.e. oleanolic acid (OA) and maslinic acid (MA), followed by a biological evaluation of the novel α-acylamino carboxamides and the α-acyloxy carboxamides in colorimetric SRB assays to determine their cytotoxic potential. Especially, the MA-Ugi products 6a, 6b and 7b showed a remarkable cytotoxicity for A2780 ovarian carcinoma cells in a low μM range. Compounds 6a and 7b induced programmed cell death in part through the apoptosis pathway.
天然产物先导化合物与基于异腈的多组分反应（IMCRs）衍生化的前景广阔的组合，已引起人们对构建具有良好药理潜力的多样性导向库的兴趣。因此，从天然存在的三萜类化合物，即齐墩果酸（OA）和山楂酸（MA）出发，成功合成了一组34种Ugi产物和3种Passerini产物，随后通过比色SRB分析对新型α-酰基氨基羧酰胺和α-酰氧基羧酰胺进行生物学评估，以确定它们的细胞毒性潜力。特别是，MA-Ugi产物6a、6b和7b在低μM范围内对A2780卵巢癌细胞表现出显著的细胞毒性。化合物6a和7b部分通过凋亡途径诱导程序性细胞死亡。
