转化齐墩果酸为米托卡宁，具有纳摩尔细胞毒性的双模态作用的罗丹明 B 缀合物。

Transformation of asiatic acid into a mitocanic, bimodal-acting rhodamine B conjugate of nanomolar cytotoxicity.

机构信息

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany.

出版信息

Eur J Med Chem. 2018 Nov 5;159:143-148. doi: 10.1016/j.ejmech.2018.09.066. Epub 2018 Sep 26.

DOI:10.1016/j.ejmech.2018.09.066

Abstract

Based on their biological activity natural products continue to represent optimal lead structures for the development of novel drug candidates. We focused on the syntheses of several derivatives of the triterpene asiatic acid and on the evaluation of their cytotoxic activity in a photometric sulforhodamin B assay. Especially, benzamide 2 and rhodamine B conjugate 11 show a distinct cytotoxicity for several human tumor cell lines, e.g. EC (A2780) = 110 ± 1 nM and EC (A2780) = 8 ± 2 nM, respectively. Interestingly, compound 11 showed for two human tumor cell lines (HT29 and 518A2) non-linear, bimodal dose-response relationships.

摘要

基于其生物活性，天然产物继续成为开发新型候选药物的最佳先导结构。我们专注于几种三萜酸衍生物的合成，并在比色磺基罗丹明 B 测定中评估它们的细胞毒性活性。特别是苯甲酰胺 2 和罗丹明 B 缀合物 11 对多种人肿瘤细胞系具有明显的细胞毒性，例如 EC（A2780）=110±1nM 和 EC（A2780）=8±2nM。有趣的是，化合物 11 对两种人肿瘤细胞系（HT29 和 518A2）表现出非线性、双模态剂量反应关系。