以VEGFR为靶点的齐墩果酸衍生物的设计、合成及抗肿瘤活性研究

宋艳玲; 刘忠岩; 李玲; 李杰; 张蓬勃

doi:10.16438/j.0513-4870.2018-0731

以VEGFR为靶点的齐墩果酸衍生物的设计、合成及抗肿瘤活性研究

Design, synthesis and anti-tumor activity studies of oleanolic acid derivatives using VEGFR as target

摘要

摘要: 以齐墩果酸（oleanolic acid，OA）为先导化合物进行结构优化，通过引入乙二胺结构单元，并以乙二胺为连接臂拼合多种生物活性片段，设计并合成了20个新的衍生物，其结构经¹H NMR、¹³C NMR和HR-MS确证。对所合成的目标化合物以人肝癌细胞（HepG2）和人胃癌细胞（SGC7901）进行体外抗肿瘤活性测试，结果表明目标化合物对两种肿瘤细胞的抑制活性均明显强于OA，其中I₆、I₈和I₉对HepG2细胞显示出较强的活性（IC₅₀=16.7、9.8和6.3 μmol·L-1）。分子模拟对接研究表明，目标化合物I₆～I₉和血管内皮生长因子受体（vascularendothelial growth factor receptor，VEGFR）蛋白具有较好的结合能力。对化合物I₆～I₉进行VEGFR-2的抑制活性测试，结果表明化合物I₉对VEGFR-2具有较强的抑制作用（IC₅₀=0.56 μmol·L-1）。

Abstract: In this study, twenty containing ethylenediamine groups derivatives of oleanolic acid (OA) were synthesized, their structures were determined by ¹H NMR, ¹³C NMR and HR-MS. The anti-tumor activities in HepG2 and SGC7901 cells were evaluated by MTT assay. The results showed that all compounds exhibited anti-tumor activity, compounds I₆, I₈ and I₉ exhibited significant anti-tumor activities with IC₅₀ values of 16.7, 9.8 and 6.3 μmol·L^-1, respectively. Molecular docking studies showed that compounds I₆-I₉ produce higher combining ability with VEGFR. Compound I₆-I₉ were further evaluated for the inhibitory activity against VEGFR-2, the result showed I₉ had a strong inhibitory effect on VEGFR with IC₅₀ values of 0.56 μmol·L^-1.

HTML全文

参考文献(19)

施引文献

资源附件(0)