异土木香内酯及土木香内酯的结构修饰研究  

Structural Modification of Isoalantolactone and Alantolactone Isolated from Inula helenium

作　　者：杜会静[1] 史海明[1] 王梦月[1] 彭崇胜[1] 李晓波[1] 

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《天然产物研究与开发》2013年第2期156-160,共5页Natural Product Research and Development

基　　金：国家科技重大专项"重大新药创制"项目(2009ZX09502-013;2012ZX09103201-038);上海交通大学"晨星青年学者奖励计划"(A10CX60)

摘　　要：对土木香根中两个主要倍半萜内酯-异土木香内酯(1)和土木香内酯(2)进行结构修饰,研究结构修饰产物的体外抑制人肝癌细胞(HepG2)增殖的活性,并进行构效关系的研究。经结构修饰得到4,15β-环氧异土木香内酯(1b)、5α,6α-环氧土木香内酯(2b)、13α-甲氧基甲基土木香内酯(2d)等11个化合物,其中产物2d未见有文献报道。产物1b、2b对HepG2细胞的抑制作用均强于母体化合物,其他化合物的抑制活性均弱于母体化合物。推断11,13-去氢内酯基团是该类倍半萜内酯体外抑制HepG2肿瘤细胞增殖活性必需的活性基团,环氧基团的引入对化合物的抑制HepG2肿瘤细胞增殖活性具有促进作用。The objective of this study was to modify the structures of isoalantolactone （1） and alantolactone （2）. All the derivatives were screened for antiproliferative activity against HepG2 cell line in vitro to explore the structure-antiproliferative activity relationship. In total, 11 compounds were obtained, of which 13ct-methoxymethyl-alanlactone （2d） was reported for the first time. The results showed that epoxyisoalantolactone （lb） and 5a,6aepoxyalantolactone （2b） performed higher antiproliferative activity against HepG2 than compounds 1 and 2 while others performed weaker. Hence it was speculated that the 11,13-dehydrolactone fraction played a key role in keeping the antiproliferative activity against HepG2 cancer cells and the addition of an oxygen atom to form an epoxy group on the skeleton of isoalantolactone （ 1 ） and alantolactone （2） could further stimulate the antiproliferative activity.

关 键 词：土木香 异土木香内酯 土木香内酯 结构修饰 抗增殖活性 

分 类 号：R284.3[医药卫生—中药学]