Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str 2, D-06120 Halle, Saale, Germany.
Eur J Med Chem. 2011 Nov;46(11):5356-69. doi: 10.1016/j.ejmech.2011.08.038. Epub 2011 Aug 31.
Triterpenoic acids show many pharmacological effects, among them an antiinflammatory or an antitumor activity. One of these, glycyrrhetinic acid (1) is of interest because of its antitumor profile. Glycyrrhetinic acid is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize new derivatives of it--differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/ethidium bromide assay and trypan blue staining. The most active compound, 34, a benzyl glycyrrhetinate holding an extra 3-N-(3-aminopropyl)glycyl substituent showed IC(50) between 1.96 and 5.14 μm for five human cancer cell lines and triggers apoptosis in 80% of the cells.
三萜酸显示出许多药理作用，其中包括抗炎或抗肿瘤活性。其中一种，甘草次酸（1）因其抗肿瘤特性而受到关注。甘草次酸不仅具有细胞毒性，而且还能在各种人类肿瘤细胞系中引发细胞凋亡。为了提高母体 1 的细胞毒性，我们着手合成其结构和脂溶性不同的新衍生物。这些化合物在磺基罗丹明 B 测定法中进行了细胞毒性测试，并通过吖啶橙/溴化乙锭测定法和台盼蓝染色筛选其诱导细胞凋亡的能力。最活性的化合物 34，一种带有额外的 3-N-(3-氨基丙基)甘氨酰取代基的苄基甘草次酸，对五种人类癌细胞系的 IC50 在 1.96 到 5.14μm 之间，能诱导 80%的细胞凋亡。
