Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany.
University of Nizwa, Chair of Oman's Medicinal Plants and Marine Natural Products, P.O. Box 33, PC 616, Birkat Al-Mauz, Nizwa, Oman.
Eur J Med Chem. 2018 Jul 15;155:869-879. doi: 10.1016/j.ejmech.2018.06.051. Epub 2018 Jun 27.
Parent pentacyclic triterpenoic acids such as ursolic-, oleanolic, glycyrrhetinic, betulinic and boswellic acid were converted into their acetylated piperazinyl amides that were coupled with rhodamine B. SRB assays to evaluate their cytotoxicity showed all of these triterpene-homopiperazinyl-rhodamine adducts 16-20 being highly cytotoxic for a panel of human tumor cell lines even in nanomolar concentrations while being significantly less cytotoxic for non-malignant cells. Interestingly enough, these compounds were even more cytotoxic than previously prepared piperazinyl analogs, thus making the homopiperazinyl spacer a very interesting scaffold for the development of biologically active compounds. Extra staining experiments showed that the cytostatic effect of compounds 18 and 20 onto A2780 cancer cells is due to their ability to act as a mitocan.
双亲环三萜酸如熊果酸、齐墩果酸、甘草次酸、白桦酸和乳香酸被转化为它们的乙酰化哌嗪酰胺，然后与若丹明 B 偶联。SRB 测定法评估其细胞毒性的结果表明，所有这些三萜-同哌嗪基-若丹明加合物 16-20 对一组人肿瘤细胞系均具有高度的细胞毒性，即使在纳摩尔浓度下也是如此，而对非恶性细胞的细胞毒性则明显降低。有趣的是，这些化合物比以前制备的哌嗪类似物更具细胞毒性，因此使得同哌嗪基间隔物成为开发生物活性化合物的非常有趣的支架。额外的染色实验表明，化合物 18 和 20 对 A2780 癌细胞的细胞生长抑制作用是由于它们能够作为一种线粒体靶向药物。
