新型蓝萼甲素-噻唑类衍生物的设计、合成与生物学评价
收稿日期: 2021-01-31
修回日期: 2021-02-26
网络出版日期: 2021-03-09
基金资助
国家自然科学基金(21672182); 河南省科技攻关(212102311026); 国家大学生创新创业训练计划(202010472018)
Design, Synthesis and Biological Evaluation of Novel Thiazole-Fused Glaucocalyxin A Derivatives
Received date: 2021-01-31
Revised date: 2021-02-26
Online published: 2021-03-09
Supported by
National Natural Science Foundation of China(21672182); Science and Technology Tackling Key Project of Henan Province(212102311026); National Undergraduate Training Program for Innovation and Entrepreneurship(202010472018)
蓝萼甲素(Glaucocalyxin A, GLA)是从蓝萼香茶菜中分离得到的四环二萜类活性天然产物. 设计并合成了一系列基于蓝萼甲素的噻唑类衍生物, 评估了它们对六种肿瘤细胞(HepG2, NCI-H460, JEG-3, K562, HL-60和Hela)的增殖抑制活性. 结果表明在GLA的A环上引入氨基噻唑结构可以显著提高其细胞增殖抑制活性, 尤其是N-烷基氨基噻唑类衍生物对六种肿瘤细胞都表现出较好的抑制活性. 其中, 化合物6和8对HL-60和Hela细胞的抑制活性都优于阳性药物阿霉素, IC50低至0.51 µmol•L –1. 形态学和流式细胞仪的测定表明蓝萼甲素-噻唑类化合物可以诱导肿瘤细胞凋亡.
张涛 , 李念先 , 周楠茜 , 马雯 , 卫海沅 , 张冰欣 , 陈亮辉 , 海广范 , 段迎超 , 白素平 . 新型蓝萼甲素-噻唑类衍生物的设计、合成与生物学评价[J]. 有机化学, 2021 , 41(6) : 2393 -2400 . DOI: 10.6023/cjoc202101058
Glaucocalyxin A (GLA) is an active natural tetracyclic diterpenoid isolated from the traditional Chinese herb Isodon glaucocalyx (maxin) Hara. In this work, a series of thiazole type derivatives based on GLA were designed and prepared. Their antiproliferative activities against six tumor cell lines (HepG2, NCI-H460, JEG-3, K562, HL-60 and Hela) were evaluated in-vitro. The results revealed that the introduction of aminothiazole substructures into A-ring of the GLA could improve their antiproliferative effects significantly. Among them,N-alkyl thiazole derivatives showed remarkably activities to the six tumor cell lines. Especially, compounds6and8presented significant antitumor activities against HL-60 and Hela cell lines with IC50 as low as 0.51 µmol•L –1, which were better than the positive drug adriamycin. The apoptosis morphology and flow cytometry studies indicated that the thiazole-fused GLA derivatives could induce apoptosis of tumor cells.
Key words： glaucocalyxin A; thiazole; antitumor
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