齐墩果酸和熊果酸衍生物的合成、表征及抗癌活性的研究
收稿日期: 2015-09-01
修回日期: 2015-10-30
网络出版日期: 2015-12-15
基金资助
国家自然科学基金(No.21101067)资助项目.
Synthesis, Characterization and Anticancer Activity of Oleanolic Acid and Ursolic Acid Derivatives
Received date: 2015-09-01
Revised date: 2015-10-30
Online published: 2015-12-15
Supported by
Project supported by the National Natural Science Foundation of China (No. 21101067).
根据拼合原理,以天然产物齐墩果酸和熊果酸作为先导化合物,通过丁二酸连接片段,在C-28位分别导入哌嗪、N-甲基哌嗪及吗啉片段,共设计、合成了12种未见文献报道的齐墩果酸和熊果酸衍生物.利用IR、1H NMR、13C NMR和HRMS等波谱技术对所合成的目标化合物进行了结构表征,并采用3-(4,5-二甲基-2-噻唑)-2,5-二苯基溴化四氮唑噻唑蓝(MTT)法观察其对癌细胞的抑制作用,结果表明化合物OA-4、OA-7、OA-8a、OA-8b、UA-4、UA-7、UA-8a和UA-8b对人乳腺癌细胞(MCF-7)、人宫颈癌细胞(Hela)和人肺腺癌细胞(A549)的抑制作用远优于先导化合物齐墩果酸和熊果酸,且OA-4,OA-7,UA-4和UA-7与阳性对照物Gefitinib的IC50值相当.
陈艳华 , 侯熙彦 , 支德福 , 李常 , 田甜 , 孙竞阳 , 赵龙铉 , 赵春晖 . 齐墩果酸和熊果酸衍生物的合成、表征及抗癌活性的研究[J]. 有机化学, 2016 , 36(4) : 795 -802 . DOI: 10.6023/cjoc201509002
Based on the combination principle, twelve novel oleanolic acid and ursolic acid derivatives were designed and synthesized through introduction of piperazine, N-methyl piperazine and morpholine moiety in C-28 position. Structures of all target compounds were characterized by IR, 1H NMR, 13C NMR and HRMS. Their in vitro anticancer activities towards MCF-7, Hela and A549 cell lines were evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results indicate that OA-4, OA-7, OA-8a, OA-8b, UA-4, UA-7, UA-8a and UA-8b against MCF-7, Hela and A549 cells are obviously better than OA and UA, OA-4, OA-7, UA-4 and UA-7 are equally as well the IC50 of positive control gefitinib.
Key words： oleanolic acid; ursolic acid; piperazine; anticancer activity
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