常春藤皂苷元衍生物的合成和抗肿瘤活性
收稿日期: 2022-04-07
修回日期: 2022-05-25
网络出版日期: 2022-06-09
基金资助
国家自然科学基金(81960626); 国家自然科学基金(82160666); 国家自然科学基金(82160628); 中国吉林省教育厅(JJKH 20191156KJ)
Synthesis and Antitumor Activity of Hederagenin Derivatives
Received date: 2022-04-07
Revised date: 2022-05-25
Online published: 2022-06-09
Supported by
National Natural Science Foundation of China(81960626); National Natural Science Foundation of China(82160666); National Natural Science Foundation of China(82160628); Jilin Provincial Education Department of China(JJKH 20191156KJ)
以常春藤皂苷元为先导化合物, 设计并合成了三个系列的含有各种杂环的新型常春藤皂苷元衍生物, 并利用1H NMR, 13C NMR和HRMS对其结构进行了表征. 通过噻唑蓝(MTT)方法评估了这些化合物对人非小细胞肺癌细胞(A549)、人乳腺癌细胞(MCF-7)、人结肠癌细胞(HCT116)、人结肠癌细胞(SW620)、人肝癌细胞(HepG-2)和人肝癌细胞(BEL7402)的体外抗肿瘤活性. 实验结果表明, (3β,4α)-3,23-二羟基齐墩果-12-烯-28-酸-[1-(4-硝基苯基)-1H-1,2,3-三唑-4-基]甲酯(A5)对HCT116细胞的抗增殖活性最强(IC50=2.05 μmol/L). 蛋白印迹实验表明, 化合物A5可能通过NF-κB信号通路发挥其抗肿瘤活性.
黄兴 , 张昌浩 , 邓浩 , 沈庆坤 , 郭红艳 , 全哲山 , 李志勇 , 金莉莉 . 常春藤皂苷元衍生物的合成和抗肿瘤活性[J]. 有机化学, 2022 , 42(9) : 2877 -2887 . DOI: 10.6023/cjoc202204021
Using hederagenin as lead compound, three series of novel hederagenin derivatives containing various heterocycles were designed and synthesized. Their structures were characterized by 1H NMR, 13C NMR and HRMS. The in vitro antitumor activities of these compounds on human non-small cell lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HCT116), human colon cancer cells (SW620), human hepatoma cells (HepG-2) and human hepatoma cells (BEL7402) were evaluated by thiazolyl blue (MTT) method. The experimental results showed that (3β,4α)-3,23-dihydroxy- olean-12-ene-28-acid-(1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl ester (A5) had the strongest anti-proliferative activity (IC50=2.05 μmol/L) on HCT116 cells. Western blotting experiments showed that compound A5 may exert its antitumor activity through NF-κB signaling pathway.
Key words： hederagenin; anticancer; thiazolyl blue (MTT) assay; Western blotting
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