摘要
目的设计并全合成7-芳杂环高喜树碱衍生物并测试抗肿瘤活性。方法首先合成关键中间体5-乙基-5-羟基-4,5,8,9-四氢氧杂环庚三烯并[3,4-f]中氮茚-3,7,11(1H)-三酮,经Frilander反应得到7-氯甲基-10-甲基高喜树碱,然后与芳杂环生成目标产物。结果与结论合成了3个新化合物,化合物的结构经1H-NMR、FAB-MS谱确证,体外抗肿瘤活性测试结果显示化合物7和8c对肿瘤细胞A549、LOVO和MCF-7具有良好的抗肿瘤活性,优于拓扑替康。
Aim To design and synthesize 7-heteroaromatic homocamptothecin derivatives to screen more potent antitumor agents. Methods The target compounds were synthesized by Frilander condensation from heteroaromatic compounds and 7-chloromethyl homocamptothecin（7） which was obtained from 5-ethyl-5- hydroxy-4,5, 8, 9-tetrahydrooxocycloheptatriene- [ 3, 4-f ]-indolizin-3, 7, 11 （ ^1H ）-trione （6）. Results and conclusion Three new compounds were synthesized and their structures were characterized by ^1H-NMR and FAB-MS. Antitumor activity tests in vitro indicated that compound 7 and 8c possessed higher inhibiting activity against A-549, LOVO and MCF-7 cell lines than topotecan.
出处
《中国药物化学杂志》
CAS
CSCD
2008年第2期105-108,共4页
Chinese Journal of Medicinal Chemistry
基金
上海市科委重点科技攻关项目(064319009)
关键词
高喜树碱
合成
抗肿瘤活性
homocamptothecin
synthesis
antitumor activity
