Synthesis and Evaluation of Gambogic Acid Derivatives as Antitumor Agents. Part III
Synthesis and Evaluation of Gambogic Acid Derivatives as Antitumor Agents. Part III
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DOI：
10.1002/cbdv.201200126
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发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
You, Qi-Dong
中科院分区：
文献类型：
--
作者：
Guo, Xiao-Ke;Sun, Hao-Peng;You, Qi-Dong
藤黄酸（GA）是一种有效的细胞凋亡诱导剂。以前，我们已经报道了在GA的C（34）和C（39）处的化学修饰，导致一些具有改进活性的试剂。去研究进一步的结构？活性关系（SAR）和GA活性机理的初步研究，合成了一系列GA异戊烯基侧链修饰的衍生物，并对其活性进行了评价。大多数衍生物对HepG 2和A549细胞株的增殖具有较强的抑制活性。化合物4由于其突出的活性而被选择用于进一步的机理研究。通过Annexin-V/PI双染色和Western blot分析，证实化合物4诱导HepG 2细胞凋亡，因此，化合物4可以作为开发新的抗肿瘤细胞凋亡的先导化合物。
Gambogic acid (GA) has been reported as a potent apoptosis inducer. Previously, we have reported chemical modification at C(34) and C(39) of GA, leading to some agents with improved activity. To investigate the further structure?activity relationship (SAR) and preliminary mechanism of GA activity, a series of derivatives with modified prenyl side chains of GA were synthesized and evaluated. Most of the derivatives showed potent inhibitory activities against the proliferation of HepG2 and A549 cell lines. Compound 4 was selected for further mechanistic studies due to its outstanding activity. It was established that 4 induces the apoptosis of HepG2 cells by using Annexin-V/PI double staining and Western blot assay, thus, compound 4 can serve as a promising lead compound for the development of novel apoptosis in anticancer treatment.