Sommerwerk Sven, Heller Lucie, Kerzig Christoph, Kramell Annemarie E, 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. 2017 Feb 15;127:1-9. doi: 10.1016/j.ejmech.2016.12.040. Epub 2016 Dec 23.
Triterpenoic acids 1-6 exhibited very low or no cytotoxicity at all, but their corresponding 2,3-di-O-acetyl-piperazinyl amides 13-18 showed low EC values for several human tumor cell lines. Their cytotoxicity, however, was also high for the non-malignant mouse fibroblasts NIH 3T3. A significant improvement was achieved by preparing the rhodamine B derivatives 19-24. While rhodamine B is not cytotoxic (up to a concentration of 30μM - cut-off of the assay), the triterpenoid piperazine-spacered rhodamine B derivatives were cytotoxic in nano-molar concentration. Compound 24 (a diacetylated maslinic acid derivative) was most toxic for several human tumor cell lines but less toxic for mouse fibroblasts NIH 3T3. Staining and double-staining experiments revealed 24 to act as a mitocan.
三萜酸1 - 6表现出极低的细胞毒性或完全没有细胞毒性，但它们相应的2,3 - 二 - O - 乙酰基 - 哌嗪基酰胺13 - 18对几种人类肿瘤细胞系显示出较低的半数有效浓度（EC）值。然而，它们对非恶性小鼠成纤维细胞NIH 3T3的细胞毒性也很高。通过制备罗丹明B衍生物19 - 24实现了显著的改进。虽然罗丹明B没有细胞毒性（在高达30μM的浓度 - 该检测的截止浓度），但三萜类哌嗪间隔的罗丹明B衍生物在纳摩尔浓度下具有细胞毒性。化合物24（一种二乙酰化齐墩果酸衍生物）对几种人类肿瘤细胞系毒性最大，但对小鼠成纤维细胞NIH 3T3毒性较小。染色和双重染色实验表明24作为一种线粒体靶向药物起作用。
