西柏三烯-4,6-二醇衍生物的合成及抗肿瘤活性  

Synthesis and Antitumor Activities of α-2,7,11-Cembratriene-4,6-diol Derivatives

作　　者：白冰 王龙 徐改改 杨鹏飞 张改红 毛多斌 BAI Bing;WANG Long;XU Gaigai;YANG Pengfei;ZHANG Gaihong;MAO Duobin(School of Food&Biological Engineering,Zhengzhou University of Light Industry,Zhengzhou 450000,China)

机构地区：[1]郑州轻工业大学食品与生物工程学院

出　　处：《高等学校化学学报》2020年第3期481-489,共9页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21476216);国家烟草专卖局行业重点实验室基金(批准号:中烟办[2014]334号)资助~~

摘　　要：以烟草中含量丰富的大环二萜类化合物2,7,11-西柏三烯-4,6-二醇(CBT)为母体,其C6位羟基经酯化/醚化,合成了28个西柏三烯-4-醇-6-羧酸酯及西柏三烯-4-醇-6-烷氧类化合物.采用核磁共振波谱(NMR)和高分辨质谱(HRMS)对目标化合物进行了结构表征,并初步评价了其生物活性.细胞毒活性测试结果表明,部分化合物对肿瘤细胞的抑制作用与阳性对照顺铂相当,其中α-2,7,11-西柏三烯-4-醇-6-O-苯乙酸酯(1 i)对乳腺癌细胞株MCF-7的IC 50值为15.45μmol/L,α-2,7,11-西柏三烯-4-醇-6-O-(2-氟)苯乙酸酯(1 t)对肺癌细胞株SMMC-7721的IC 50值为11.44μmol/L.Twenty eightα-2,7,11-cembratriene-4,6-diol derivatives were prepared by the modification at C6 position via introduction of acyl and ether groups.Their structures were confirmed by nuclear magnetic resonance spectroscopy(NMR)and high resolution mass spectrometry(HRMS).The synthesized compounds were screened for their in vitro biological activity.The results of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2 H-tetrazolium(MTS)assay indicated that some of them showed the same anticancer activity as cisplatin(DDP)did.Among them,α-2,7,11-cembratriene-4-ol-6-phenylacetate(1 i)showed cytotoxicity against MCF-7 with an IC 50 value of 15.45μmol/L,andα-2,7,11-cembratriene-4-ol-6-(2-F)phenylacetate(1 t)showed cytotoxicity against SMMC-7721 with an IC 50 value of 11.44μmol/L,respectively.Structure-activity relationship revealed that the phenylacetate substituents at C6 position played an important role in inhibition activity.

关 键 词：西柏三烯衍生物 抗肿瘤 烟草 

分 类 号：O629.9[理学—有机化学]