Jin Yan, Sun Yuhong, Yu Yue, Zhao Jiao, Zheng Mingshan, Wang Liming, Jin Ying
Department of Pharmacy, Jilin Medical University, Jilin 132013, China.
College of Science, Yanbian University, Yanji 133000, China.
Molecules. 2025 Jan 4;30(1):172. doi: 10.3390/molecules30010172.
An efficient stereoselective synthesis of 10-hydroxy-10-(1-indol-3-yl)-9-(10)-phenanthrene derivatives was realized through an organocatalyzed Friedel-Crafts reaction of phenanthrenequinones and indoles using a (,)-dimethylaminocyclohexyl-squaramide as the catalyst. Under the optimized conditions, the desired chiral products were obtained in good yields (73-90%) with moderate to high ee values (up to 97% ee). Two pairs of synthesized enantiomers were subjected to evaluation of their antiproliferative activities on four types of human cancer cell lines and one human umbilical vein endothelial cell line using the CCK-8 assay. The results indicated that stereoselectivity had obvious impacts on biological activity. ()- was found to have optimal cytotoxicity against the A549 cell line and a good safety profile for human normal cells, which was better than the inhibitory activity of the positive control drug (doxorubicin).
通过使用（，）-二甲基氨基环己基方酰胺作为催化剂，菲醌与吲哚进行有机催化的傅克反应，实现了10-羟基-10-（1-吲哚-3-基）-9-（10）-菲衍生物的高效立体选择性合成。在优化条件下，以中等至较高的对映体过量值（高达97% ee）获得了高产率（73-90%）的所需手性产物。使用CCK-8测定法对两对合成的对映体在四种人类癌细胞系和一种人脐静脉内皮细胞系上的抗增殖活性进行了评估。结果表明，立体选择性对生物活性有明显影响。发现（）-对A549细胞系具有最佳细胞毒性，对人类正常细胞具有良好的安全性，优于阳性对照药物（阿霉素）的抑制活性。
