土木香中纯化的五种倍半萜类化合物抑制肿瘤增殖活性的研究

In vivo and in vitro anti-tumor activity studies of five sesquiterpenoids from Inula helenium

目的检测土木香中纯化的五种倍半萜化合物抑制肿瘤增殖的活性,并探讨化合物结构与活性之间的关系。方法应用MTT法测定五种倍半萜类化合物对体外培养人肿瘤细胞增殖的影响;应用小鼠移植性肝癌模型测定了异土木香内酯的抗肿瘤活性。结果化合物1(异土木香内酯)对U251SP细胞、HLE细胞和MM1-CB细胞的增殖显示较强的抑制活性;化合物2～5对各种实验用肿瘤细胞的增殖不显示抑制活性;化合物1对移植性肿瘤(肝癌H22)具有明显的抑制作用,并呈现较好的剂量依赖关系。结论异土木香内酯具有较强的肿瘤抑制活性;化合物2～5对肿瘤细胞增殖抑制活性丧失可能由于A-环和B-环之间的键裂开,形成一个大10元环,改变了原来的构象所致。

Aim To detect the antitumor activities of five sesquiterpene lactones from the roots of Inula helenium. Method Using MTT assay to evaluate the anti-tumor activities of five sesquiterpene lactones to the cell lines of U251SP,T-98,HLE,MM1-CB,HMV-1 and KT,and to explore the relationship between structure and activities. Results Isoalantolactone exhibited significant anti-growth activities to U251SP,HLE and MM1-CB,while other compounds demonstrated weak or moderate anti-growth activities to cell lines even in the 50% inhibition concentration≤100 μmol·L-1. Con-clusion Isoalantolactone exhibits significant anti-growth activities to three cell lines and its anti-tumor activitiesve close relationship with the structures,α,β-unsaturated five-membered lactone ring is necessary for the activities,and saturated lactone or 5,10-seco and A,B-ring become a ten-membered macro-ring leading to the loss or decrease of anti-growth activity.