毛叶假鹰爪素CB环衍生物的合成与抗肿瘤活性评价  

Synthesis and Antitumor Evaluation of Desmosdumotin C Derivatives on B-Ring

作　　者：厉恩振[1,2] 宋明玉[1] 向卓[1,3] 张学辉[1] 韦林毅[1] 史宁[1] 吴久鸿[1,2] 

机构地区：[1]解放军第306医院药学部,北京100101 [2]军事医学科学院毒物药物研究所,北京100850 [3]第四军医大学药学院,西安710032

出　　处：《中国药学杂志》2013年第11期924-929,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30572212;81072546)

摘　　要：目的合成具有抗肿瘤活性的毛叶假鹰爪素C的B环衍生物。方法以2,4,6-三羟基苯乙酮为原料,经甲基化、O-甲基化、羟醛缩合3步反应制得目标产物,并以6个人肿瘤细胞株进行抗增殖活性评价。结果制备了14个目标化合物,其中9个为新化合物。经1H-NMR、13C-NMR,MS确证结构。结论初步活性研究表明,除1i的目标化合物均具有一定程度的抗肿瘤活性,1h和1n活性优于毛叶假鹰爪素C,B环引入两个F原子对化合物抗肿瘤活性具有一定贡献。OBJECTIVE To synthesize desmosdumotin C derivatives on B-ring with antitumor activity. METHODS The target compounds were synthesized from 2,4,6-trihydroxyacetophenone via methylation, O-methylation and aldol reaction. Their antiproliferarive activities were tested against six human tumor cell lines. RESULTS Fourteen target compounds were synthesized, nine of which were new compounds. All of them were characterized using 1H-NMR, 13 C-NMR and MS. CONCLUSION Preliminary pharmacological test showed that all the title compounds except li exhibited potent antitumor activities,1h and 1n were better than desmosdumotin C in vitro. Introducing two fluoro atom on B-ring would benefit its activity against some tumor cells.

关 键 词：毛叶假鹰爪素C衍生物 合成 体外抗肿瘤活性评价 

分 类 号：R914[医药卫生—药物化学]