Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
Bioorg Med Chem. 2011 Aug 1;19(15):4421-36. doi: 10.1016/j.bmc.2011.06.047. Epub 2011 Jun 21.
A three-step transformation of ecteinascidin 770 (1b) into 2'-N-indole-3-carbonyl derivative 3 via 18,6'-O-bisallyl-protected derivative 4a, which was shown to have higher cytotoxicity than 1b, is presented. In addition, a number of 2'-N amide derivatives of 1b have been prepared from 4a and their in vitro cytotoxicity were determined by measuring IC₅₀ values against human cell lines HCT116, QG56, and DU145. Benzoyl amide derivatives 7a-c showed similar in vitro cytotoxicity to 1b, whereas the nitrogen-containing heterocyclic derivatives 7d-h and cinnamoyl derivatives 9a-b showed higher cytotoxicity than 1b. In contrast, the 18,6'-O-bisallyl protected derivatives 4a-c, 6a-h, and 8a-b showed dramatic decreases in cytotoxicity relative to 1b.
本文报道了依托泊苷 770（1b）经三步转化为 2′-N-吲哚-3-甲酰基衍生物 3 的过程，其中 18,6′-O-双烯丙基保护的衍生物 4a 显示出比 1b 更高的细胞毒性。此外，还从 4a 制备了一系列 1b 的 2′-N 酰胺衍生物，并通过测定其对 HCT116、QG56 和 DU145 人细胞系的 IC₅₀ 值来确定其体外细胞毒性。苯甲酰酰胺衍生物 7a-c 显示出与 1b 相似的体外细胞毒性，而含氮杂环衍生物 7d-h 和肉桂酰衍生物 9a-b 则显示出比 1b 更高的细胞毒性。相比之下，18,6′-O-双烯丙基保护的衍生物 4a-c、6a-h 和 8a-b 的细胞毒性相对于 1b 显著降低。
