Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes Street 2, D-06120 Halle, Germany.
Medical and Life Science Faculty, Institute of Precision Medicine, Furtwangen University, Jakob-Kienzle-Street 17, D-78054 Villigen-Schwenningen, Germany.
Molecules. 2020 Nov 20;25(22):5443. doi: 10.3390/molecules25225443.
The combination of the "correct" triterpenoid, the "correct" spacer and rhodamine B () seems to be decisive for the ability of the conjugate to accumulate in mitochondria. So far, several triterpenoid rhodamine B conjugates have been prepared and screened for their cytotoxic activity. To obtain cytotoxic compounds with EC values in a low nano-molar range combined with good tumor/non-tumor selectivity, the Rho B unit has to be attached via an amine spacer to the terpenoid skeleton. To avoid spirolactamization, secondary amines have to be used. First results indicate that a homopiperazinyl spacer is superior to a piperazinyl spacer. Hybrids derived from maslinic acid or tormentic acid are superior to those from oleanolic, ursolic, glycyrrhetinic or euscaphic acid. Thus, a tormentic acid-derived conjugate , holding a homopiperazinyl spacer can be regarded, at present, as the most promising candidate for further biological studies.
“正确”的三萜、“正确”的间隔基与若丹明 B（rhodamine B）的结合似乎对缀合物在线粒体中积累的能力起着决定性作用。迄今为止，已经制备并筛选了几种三萜若丹明 B 缀合物以研究其细胞毒性。为了获得 EC 值在低纳摩尔范围内的具有细胞毒性的化合物，同时保持良好的肿瘤/非肿瘤选择性，Rho B 单元必须通过胺间隔基连接到萜烯骨架上。为了避免螺内酰胺化，必须使用仲胺。初步结果表明，同哌嗪基间隔基优于哌嗪基间隔基。来源于齐墩果酸或熊果酸的杂种优于来源于乌苏酸、熊果酸、甘草次酸或羽扇豆酸的杂种。因此，目前认为来源于熊果酸的具有同哌嗪基间隔基的缀合物是进一步进行生物学研究的最有前途的候选物。
