新型鬼臼毒素衍生物的合成及其抗肿瘤活性  

Synthesis and antitumor activities of podophyllotoxin derivatives

作　　者：陆艳玲[1,2] 左松[1,2] 师少宇[2] 李新超[2] 张元[2] 吕晶晶[2] 陈虹[1,2,3] 

机构地区：[1]天津医科大学药学院,天津300071 [2]武警医学院生药教研室,天津300162 [3]天津职业病与环境危害生物标记重点实验室,天津300162

出　　处：《中国药物化学杂志》2010年第2期90-95,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30873363);天津市应用基础重点项目(06YFJZJC02700);天津市应用基础项目(08JCYBJC070000)

摘　　要：目的设计并合成新型鬼臼毒素类衍生物。方法5-甲氧基吲哚与氯代物或酰氯反应得到一位氮取代的5-甲氧基吲哚;其与草酰氯反应,再以4-氨基4-脱氧表鬼臼毒素为原料,经缩合反应得到目标化合物。体外活性采用Hela细胞筛选模型进行评价。结果与结论合成了7个新化合物,其中化合物7a、7b的活性优于阳性对照依托泊苷(etoposide)。Aim To synthesize novel podophyllotoxin derivatives,and to assay their antitumor activities.Methods 5-Methoxyindole was reacted with alkyl chlorides or acyl chlorides to give N-substituted 5-methoxy-indoles.N-substituted 5-methoxyindol-3-yl glyoxyl chlorides were prepared by the reaction of various N-substituted 5-methoxyindoles with oxalyl chloride.Subsequently,it was coupled with 4-amino podophyllotoxin in the presence of triethylamine to generate the products.Hela cell line was employed to assay the cytotoxicity of these compounds in vitro.Results and conclusion Seven novel podophyllotoxin derivatives were synthesized.Two compounds（7a,7b） showed comparable cytotoxicity to that of etoposide.

关 键 词：鬼臼毒素衍生物 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]