Heller Lucie, Sommerwerk Sven, Tzschöckell Felix, Wiemann Jana, Schwarz Stefan, Siewert Bianka, Al-Harrasi Ahmed, Csuk René
Department of Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Birkat Al-Mauz, Nizwa, Sultanate of Oman.
Arch Pharm (Weinheim). 2015 Dec;348(12):889-96. doi: 10.1002/ardp.201500318. Epub 2015 Nov 9.
(18α)-Glycyrrhetinic acid (4) was prepared from (18β)-glycyrrhetinic acid (1), and the cytotoxicity of some derivatives was investigated by photometric SRB assays employing several human tumor cell lines. In summary, (18β)-1 is slightly more cytotoxic than its (18α) epimer 4, but its cytotoxicity is negligible. Higher cytotoxicity was observed for the esters 2 and 5 and for the 3-O-acetylated esters 3 and 6. Cytotoxicity was improved dramatically when the hydroxyl group at position C-3 was replaced by an amino moiety. SeO2 oxidations gave access to a novel furano-glycyrrhetinoate 15. Interestingly, its seleno analog 16 is approximately five to six times less cytotoxic for the tumor cell lines tested, and tumor/non-tumor selectivity is lost upon replacement of the oxygen by a selenium substituent.
（18α）-甘草次酸（4）由（18β）-甘草次酸（1）制备得到，并通过使用多种人类肿瘤细胞系的光度比色法SRB分析研究了一些衍生物的细胞毒性。总之，（18β）-1的细胞毒性略高于其（18α）差向异构体4，但其细胞毒性可忽略不计。酯2和5以及3-O-乙酰化酯3和6表现出更高的细胞毒性。当C-3位的羟基被氨基取代时，细胞毒性显著提高。二氧化硒氧化得到一种新型呋喃-甘草次酸酯15。有趣的是，其硒类似物16对所测试的肿瘤细胞系的细胞毒性约低五到六倍，并且在用硒取代基取代氧后失去了肿瘤/非肿瘤选择性。
