Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents
Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents
复制标题
强效抗肿瘤药物菲并吲哚里西啶和菲喹里西啶生物碱的合成及比吸收率研究
DOI：
10.1016/j.ejmech.2012.02.048
复制
发表时间：
2012-05-01
影响因子：
6.7
通讯作者：
Wang, Qingmin
中科院分区：
文献类型：
--
作者：
Wang, Ziwen;Wu, Meng;Wang, Qingmin
制备了一系列菲并吲哚里西啶和菲喹啉西啶生物碱及其14-氨基衍生物(1-44)，并系统评价了它们对A549和HL60细胞系的抗肿瘤活性。生物测定结果表明，这些生物碱大部分具有良好的抗肿瘤活性。特别是，化合物15、22、28、33-36、40和42显示出低纳摩尔或亚纳摩尔水平的抗肿瘤活性。 (13aS,14S)-14-羟基菲并吲哚西啶和(14aR,15R)-15-羟基菲喹啉西啶的构型被证实是最佳的。极性增加的14-氨基菲并吲哚里西啶类化合物具有良好的抗肿瘤活性，尤其是化合物26和28。大多数菲并喹啉西啶生物碱比菲并吲哚里西啶生物碱表现出更高的抗肿瘤活性。我们目前的研究为菲并吲哚里西啶和菲喹啉西啶生物碱作为潜在抗肿瘤药物的开发和优化提供了基础支持。 (C) 2012 Elsevier Masson SAS。版权所有。
A series of phenanthroindolizidine and phenanthroquinolizidine alkaloids and their 14-amino-derivatives (1-44) were prepared and systematically evaluated for their anti-tumor activities against A549 and HL60 cell lines. The bioassay results showed that most of these alkaloids possess good anti-tumor activities. Especially, compounds 15, 22, 28, 33-36, 40 and 42 displayed low nanomolar or subnanomolar levels of anti-tumor activity. The configuration of (13aS,14S)-14-hydroxyphenanthroindolizidines and (14aR,15R)-15-hydroxyphenanthroquinolizidines was confirmed to be optimal. 14-Amino-phenanthroindolizidines with increased polarity possess good anti-tumor activity, especially for compounds 26 and 28. Most of the phenanthroquinolizidine alkaloids exhibited higher anti-tumor activity than that of phenanthroindolizidine alkaloids. Our present study provides fundamental support for development and optimization of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anti-tumor drugs. (C) 2012 Elsevier Masson SAS. All rights reserved.