靶向VEGFR抑制剂齐墩果酸类似物的合成及抗肿瘤活性研究  

Synthesis of oleanolic acid analogues targeting VEGFR inhibitors and their antitumor biological activities

作　　者：高诗特 丁明雪 邬月娇 梅宇 孟艳秋[1] GAO Shi-te;DING Ming-xue;WU Yue-jiao;MEI Yu;MENG Yan-qiu(Department of Pharmaceutical Engineering,Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]沈阳化工大学制药工程教研室,辽宁沈阳110142

出　　处：《中国药物化学杂志》2021年第11期872-880,共9页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21372156);辽宁省高等学校创新团队支持项目(LT2017009);辽宁省重点研发计划项目(2019JH2/10300034);沈阳化工大学重点攻关项目(LDB2019001);辽宁省教育厅面上项目(LJKZ0427)。

摘　　要：目的合成齐墩果酸衍生物,并进行生物活性测试与分子对接研究。方法以齐墩果酸为起始原料,设计、合成10个靶向VEGFR受体抑制剂;采用MTT法,用人肝癌细胞(HepG2)和乳腺癌细胞(MCF-7)对其进行初步体外抗肿瘤活性筛选;使用计算机辅助药物设计,确定能和关键位点结合的活性基团。结果合成了10个未见文献报道的齐墩果酸衍生物,其结构经^(1)H-NMR、^(13)C-NMR和ESI-MS谱确证。活性测试得出化合物Ⅰ_(1)、Ⅱ_(4)与阳性对照药相比有更强的抑制作用,其抗肿瘤活性高于母体齐墩果酸,分子对接结果显示Ⅱ_(4)与VEGFR受体具有较好的结合能力。结论化合物Ⅱ_(4)有成为新的VEGFR受体抑制剂潜能,值得进一步研究。In order to develop novel VEGFR inhibitors,a series of novel oleanolic acid derivatives were designed and synthesized using oleanolic acid as the starting material,based on computer-aided drug design to designed and synthesized 10 targeted VEGFR inhibitors,The compounds structures were confirmed by ^(1)H-NMR,^(13)C-NMR and ESI-MS.Human liver cancer cells(HepG2)and breast cancer cells(M CF-7)w ere used for preliminary assaying of anti-tumor activity in vitro through MTT method.The activity assay show ed that compounds Ⅰ_(1) and Ⅱ_(4) had stronger inhibitory effects than the positive control drugs gefitinib and parent oleanolic acid.The molecular docking results show ed that Ⅱ_(4) had a better binding ability to VEGFR,worthy of further study.

关 键 词：齐墩果酸衍生物 结构改造 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]