β-榄香烯吲哚衍生物的合成及其体外抗K562细胞增殖活性  

Synthesis and antiproliferative activity in K562 cells of β-elemene indole derivatives in vitro

作　　者：武芳莉[1] 唐虹 惠子[1] 刘洋[3] 徐莉英[1] 董金华[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部萤点实验室.辽宁沈阳110016 [2]辽宁卫生职业技术学院,辽宁沈阳110101 [3]福建医科大学药学院,福建福州350004

出　　处：《中国药物化学杂志》2014年第1期1-6,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家十一五“重大新药创制”科技重大专项(2009ZX09103-057);辽宁省教育厅重点实验室创新团队项目(2007T176)

摘　　要：目的设计合成β-榄香烯吲哚衍生物并进行体外抗癌活性筛选。方法通过合成β-榄香烯氯代物,在其结构中引入3-吲哚乙胺结构片段进而合成β-榄香烯吲哚衍生物。采用MTT法测定目标化合物对K562白血病细胞的增殖抑制作用。结果合成了15个未见文献报道的β-榄香烯吲哚衍生物。目标化合物的结构经1H-NMR、MS谱确证。活性实验结果显示14个目标化合物的活性高于β-榄香烯。结论在β-榄香烯结构中引入3-吲哚乙胺结构片段有利于提高此类化合物的抗癌活性。Elemene emulsion is a broad spectrum antitumor drug, whose main component is fl-elemene. Due to poor water-solubility and the requirement of high concentrations to reach therapeutic effects, the efficacy of elemene emulsion in cancer treatment is limited. To improve its activity, a series of fl-elemene indole de- rivatives were synthesized from β-elemene via chlorination and nucleophilic substitution. The products were separated with column chromatography. （1H-Indol-3-yl）ethanamines were prepared via Fischer indole syn- thesis from substituted phenylhydrazine hydochlorides and 4-chlorobutanal diethyl acetal. The structures of all target compounds were confirmed by 1H-NMR and MS. The growth-inhibitory effects of the synthesized de- rivatives against K562 cells were determined by MTT assay. The result showed that all the β-elemene indole derivatives except compound 10 possessed more potent antiproliferative activity in vitro than β-elemene.

关 键 词：Β-榄香烯 β-榄香烯吲哚衍生物 抗癌活性 MTT法 

分 类 号：R914[医药卫生—药物化学]