文献类型：期刊文献

中文题名：新型N^6-哌嗪取代腺苷衍生物的合成及其抗肿瘤活性

英文题名：Synthesis and Antitumor Activities of Novel N^6-Piperazine Substituted Adenosine Analogues

作者：周高辉[1];罗明明[1];张阳[1];于晓芹[1];陶黎明[1];徐文平[1]

机构：[1]华东理工大学药学院,上海200237

年份：2016

卷号：24

期号：4

起止页码：283

中文期刊名：合成化学

外文期刊名：Chinese Journal of Synthetic Chemistry

收录：CSTPCD;;CSCD:【CSCD_E2015_2016】；

基金：国家科技部支撑项目(2011BAE06B04)

语种：中文

中文关键词：哌嗪;腺苷衍生物;合成;Hela细胞;抗肿瘤活性

外文关键词：piperazine ; adenosine analogue ; synthesis ; Hela cells ; antitumor activitiy

摘要：以腺苷为母体,对其N6-位进行结构改造,首先经邻位双羟基保护,N6-位氯代,再在N6-位引入哌嗪环制得中间体2',3'-异丙叉-6-哌嗪嘌呤核苷(4);4与N-氯乙酰苯胺类似物(6a^6h)偶联后脱除邻位双羟基保护合成了8个新型的N6-哌嗪取代腺苷衍生物(8a^8h),其结构经1H NMR,13C NMR和HR-ESI-MS表征。采用MTT法研究了8a^8h对Hela肿瘤细胞的抑制活性。结果表明:大部分目标化合物对Hela肿瘤细胞具有较好的抑制活性,其中2-{4-[9-(3,4-二羟基-5-羟甲基-四氢呋喃-2-基)-9H-嘌呤-6-基]-哌嗪-1-基}-N-(3-氟苯基)-乙酰胺(8e)的活性最好,IC50为21.74μmol·L-1。
The intermediate, { （ 3R, 4R, 6R, 6R ） -2,2-dimethyl-6- [ 6- （ piperazin-1 -yl ） -9H-purin-9-yl ] tetrahydrofuro [ 3,4-d ] [ 1,3 ] dioxol-4-yl t methanol （4）, was synthesized by three steps including adjacent hydroxyl protection, chlorination and introduction of piperazine at N^6 position, using adenosine as starting material. Eight novel N^6-piperazine substituted adenosine analogues （8a - 8h） were synthesized by coupling reaction of 4 with 6a - 6h, then deprotection of hydroxyl. The structures were characterized by ^1H NMR, ^13C NMR and HR-ESI-MS. Biological evaluation showed that 8a - 8h exhibited antitumor activities on Hela cells, especially, 2- { 4- [ 9- （ 3,4-dihydroxy-5-hydroxymethyl-tetrahydro-fu- ran-2-yl ） -9H-purin-6-yl ] -piperazin-1 -yl } -N- （ 3-fluoro-phenyl ） -acetamide （ 8e ） exhibited the strongest inhibitory activity with IC50 of 21.74 ixmol · L^-1.