ent-贝壳杉烯糖酯类衍生物的合成及其抗肿瘤活性的研究(英文)  

Glycosylation of ent-kaurene derivatives and an evaluation of their cytotoxic activities

作　　者：邹敏[1] 余双双[1] 王可[1] 张大永[1] 吴晓明[1] 华维一[1] 

机构地区：[1]中国药科大学药物科学研究院,南京210009

出　　处：《中国天然药物》2013年第3期289-295,共7页

基　　金：supported by the National Natural Science Foundation of China(Nos.30973607,and81172934)~~

摘　　要：目的:对含有exo-亚甲基环戊酮或α-亚甲基内酯药效团的ent-贝壳杉烯类化合物进行结构修饰,以改善其活性及水溶性。方法:以甜菊苷为原料,在4位羧基接入单糖而得到目标化合物,并使用MTT法对目标化合物进行抗肿瘤活性测试。结果:化合物1b对细胞株HepG2,Bel-7402,A549,MCF-7,MDA-MB-231均表现出了较好的抑制活性,IC50分别为0.12,0.91,0.35,0.08,0.07μmol·L–1。另外,化合物3c对HepG2(IC50=0.01μmol·L–1)具有较强的抑制作用。结论:化合物1b和3c可以作为潜在的抗肿瘤化合物进行深入研究。AIM： To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an a-methylenelactone moiety. METHODS： All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay. RESULTS： Compound lb was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 lamol.L-1, respectively. Moreover, compound 3e exhibited the most potent and selective cytotoxic activity against the HepG2 cell line （IC50, 0.01 lamol.L-1）. CONCLUSION： Compounds 1b and 3c could be considered as potential anticancer candidates for further study.

关 键 词：糖基化 四环二萜 甜菊醇 异甜菊醇 甜菊苷 exo-亚甲基环戊酮 α-亚甲基内酯 抗肿瘤活性 

分 类 号：R284.3[医药卫生—中药学]