18β-甘草次酸A环官能团化衍生物的合成及抗肿瘤活性  

Synthesis of A-Ring Functional Derivatives of 18β-Glycyrrhetinic Acid and Their Antiproliferative Effect in Tumor Cells

作　　者：高振北[1] 胡君[2] 康潇[1] 许传莲[1] 巨勇[2] 

机构地区：[1]浙江理工大学生命科学学院,杭州310018 [2]清华大学化学系,生命有机磷化学及化学生物学教育部重点实验室,北京100084

出　　处：《高等学校化学学报》2012年第4期750-754,共5页Chemical Journal of Chinese Universities

基　　金：浙江省自然科学基金(批准号:Y4110320);浙江省生物医学工程“重中之重”学科开放基金(批准号:SWYX0901);国家自然科学基金(批准号:20972086)资助

摘　　要：采用化学方法对18β-甘草次酸A环进行改造,合成了一系列新型18β-甘草次酸A环官能团化衍生物.对人白血病细胞株HL-60、K562、肝癌细胞BEL-7404及乳腺癌细胞MDA-MB-231的体外抗肿瘤活性筛选结果表明,化合物5对4种肿瘤细胞系的抑制活性均强于18β-甘草次酸;构效关系分析表明,A环内烯键的形成对抑制肿瘤细胞增殖有重要影响;同时利用Hoechst33258和AO/EB染色,在荧光显微镜下观察到了细胞凋亡小体的形成.Thirteen analogues of 18β-glycyrrhetinic acid were synthesized using various chemical methods and one of them exhibited certain cytotoxicity against cell-lines of HL60 cells,K562 cells,BEL-7404 cells and MDA-MB-231,respectively,via MTT method.The results show that compound 5 with C-C bond in the A-ring of 18β-glycyrrhetinic acid has markedly antiproliferative effect on these four tumor cells compared with 18β-glycyrrhetinic acid.K562 cells with nuclear apoptotic bodies were observed after staining with Hoechst 33258 and AO/EB with flourescence microscope.

关 键 词：18Β-甘草次酸 结构改造 A环官能团化衍生物 抗肿瘤细胞增殖活性 

分 类 号：O629.61[理学—有机化学]