丁烯酸内酯二萜衍生物的制备及抗肿瘤活性研究  

Study on preparation of butenolide diterpene derivatives and their antitumor activity

作　　者：左笑菲 杨帆 张晓梅 陈凌云 赵庆 ZUO Xiao-fei;YANG Fan;ZHANG Xiao-mei;CHEN Ling-yun;ZHAO Qing(Faculty of Pharmacy,Yunnan University of Chinese Medicine,Kumnming 650500,China)

机构地区：[1]云南中医药大学中药学院,昆明650500

出　　处：《天然产物研究与开发》2020年第7期1200-1204,1258,共6页Natural Product Research and Development

基　　金：云南省科技厅-云南中医学院应用基础研究联合专项(2017FF116(-011));国家自然科学基金(81460533,81060262,21662048)。

摘　　要：采用姜科二萜类成分coronarin E(1)、hedychenone(2)和滇姜花素A(3)进行衍生化反应,制备了三个具有丁烯酸内酯结构单元的二萜衍生物4、5和7。将部分化合物进行体外细胞毒活性测试,结果表明化合物5和7对五种肿瘤细胞株均有显著的细胞毒活性,它们对肝癌细胞株SMMC-7721、肺癌细胞株A-549、乳腺癌细胞株MCF-7和结肠癌细胞株SW480的抑制活性均超过阳性对照顺铂。对化合物4、5和7进行小鼠体内抗肿瘤活性测试,结果表明三个化合物均对小鼠体内肿瘤H22和S180均有很好的抑制作用,其中化合物4对H22肿瘤的抑制活性最高,其对H22肿瘤的抑制活性为47.44%,接近阳性对照异环磷酰胺。化合物4和7对S180肿瘤的抑制活性分别为60.16%和45.20%,均超过阳性对照异环磷酰胺。Diterpenenes were widely found in Zingiberaceae family,and some of them showed various bioactivities.Our previous researches on Hedychium genus resulted in obtaining series of diterpenes with significant cytotoxic or antitumor activities.Three butenolide diterpene derivatives 4,5,and 7 were synthesized from three Zingiberaceae diterpenes,coronarin E(1),hedychenone(2) and yunnancoronarin A(3),respectively.Compound 1 underwent photooxygenation reaction in CH2Cl2 to obtain 4,in which tetraphenyl porphyrin was served as photosensitizer and in the presence of N,N-diisopropylethylamine.Similarly,Compound 2 underwent photooxygenation to get 5.Compound 3 was benzoylated to obtain 6,which was further photooxygenated to get 7.Compounds 1,2,5,6 and 7 were subjected to in vitro cytotoxicity bioassays,the result indicates that compounds 5 and 7 have significant cytotoxicity against five tumor cell lines,including human liver cancer cells SMMC-7721,human lung cancer cells A-549,human breast cancer cells MCF-7,human colon cancer cells SW480 and human leukemia cells HL-60,and their inhibitory activities against SMMC-7721,A-549,MCF-7 and SW480 cell lines were higher than that of cisplatin(positive control).Compounds 4,5 and 7 were tested for in vivo antitumor activity in mice.As a result,the three compounds showed significant inhibitory effect on H22 and S180 tumor in mice.Compounds 4 had the strongest inhibitory effect,and its inhibitory rate on H22 was 47.44%,which was close to that of ifosfamide(positive control).Inhibitory rates of 4 and 7 on S180 were 60.16% and 45.20%,which were higher than that of ifosfamide.

关 键 词：姜科 二萜 丁烯酸内酯 抗肿瘤 细胞毒 

分 类 号：R284.1[医药卫生—中药学]