摘要/Abstract

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.
关键词: 蓝萼甲素, 噻唑衍生物, 抗肿瘤
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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