12-亚甲基脲-14-去氧穿心莲内酯衍生物的合成与抗肿瘤活性(英文)  

Synthesis and Cytotoxic Activity of 12-Methyleneurea-14-deoxyandrographolide Derivatives

作　　者：徐冲[1] 王峥涛[1] 

机构地区：[1]上海中医药大学中药研究所,上海201210

出　　处：《中国天然药物》2011年第1期46-50,共5页

基　　金：上海市科委纳米专项基金(No.0952nm05200)资助~~

摘　　要：目的:通过对穿心莲内酯引入亲水性基团,探索衍生物的抗肿瘤活性和构效关系。方法:碱性条件下,穿心莲内酯1与硝基甲烷进行Michael加成反应,重排生成12-硝基甲基-14-去氧穿心莲内酯,再以锌粉盐酸还原硝基生成12-氨基亚甲基-14-去氧穿心莲内酯2,最后与异氰酸酯反应成脲3a～3n,所有化合物考察了抗肿瘤和抑制NA活性。结果:经结构改造后,两个化合物(3f和3m)显示了中等的抗肿瘤活性,并且都是单取代芳环,提示芳环的引入优于脂肪链(环)和杂环;所有衍生物都无抑制NA活性。结论:穿心莲内酯对流感病毒神经氨酸酶无抑制活性;12位引入芳环有意义,但芳环所处的支链不能过长;水溶性基团的引入对活性提高没有帮助,具体有待进一步研究。AIM：To modify the chemical structure of andrographolide by introducing hydrophilic groups,evaluate cytotoxic activity and study the structure-activity relationship of the derivatives.METHODS：Key intermediate 2 was synthesized via Michael addition and reduction,followed by reacting with isocyanates to get 3a-3n.The compounds were evaluated for cytotoxic activity and NA （neuraminidase of H1N1） inhibition.RESULTS：Two derivatives （3f and 3m,both containing a single substituted aromatic ring） showed moderate cytotoxic activity while none of the compounds inhibited NA in the preliminary screening.CONCLUSION：Introducing aromatic ring at C-12 is advisable but the substituent can not be too large.Hydrophilic groups introduced to C-12 did not help to enhance the cyctotoxic activity,further study is in process.

关 键 词：穿心莲内酯 细胞毒活性 构效关系 合成 

分 类 号：R284.3[医药卫生—中药学]