摘要
以天然产物齐墩果酸为母体,采用计算机辅助药物设计合成齐墩果酸衍生物,对C-3、C-28位进行结构改造,合成了12个未见文献报道的靶向血管内皮生长因子受体(VEGFR)抑制剂,其结构经^(1)H NMR、^(13)C NMR谱确证。通过噻唑蓝(MTT)法采用人肝癌细胞(HepG2)和乳腺癌细胞(MCF-7)对其进行初步体外抗肿瘤活性筛选。结果表明,化合物I_(7)、II_(1)与阳性对照药相比有较强抑制作用,其抗肿瘤活性高于母体OA;分子对接结果显示I_(7)和II_(1)与VEGFR受体具有较好的结合能力,值得进一步研究。
Using the natural product oleanolic acid as the matrix,designing and synthesizing the derivative of oleanolic acid,using computer-aided drug design,the C-3 and C-28 positions were modified to design and synthesize 12 targeted VEGFR receptor inhibitors that had not been reported in the literature;Human hepatocellular carcinoma cells(HepG2)and human breast cancer cells(MCF-7)were screened for in vitro antitumor activity by Thiazole blue(MTT)method;Its structure is confirmed by ^(1)H-NMR,^(13)C-NMR spectra.The activity test showed that compounds I_(7)and II_(1)had strong inhibitory effects compared with the positive control drugs,and their antitumor activity was higher than that of the parent OA,and the molecular docking results showed that I_(7)and II_(1)had a good binding ability with the VEGFR receptor,which is worthy of further study.
作者
黄美琪
李晋明
孟贝贝
王芷琦
孟艳秋
Huang Meiqi;Li Jinming;Meng Beibei;Wang Zhiqi;Meng Yanqiu(College of Pharmaceutical and Bioengineering,Shenyang University of Chemical Technology,Shenyang,110142)
出处
《化学通报》
CAS
CSCD
北大核心
2023年第11期1363-1370,共8页
Chemistry
基金
国家自然科学基金项目(21372156)
辽宁省重点研发计划项目(2019JH2/10300034)
辽宁省教育厅项目(LJKZ0427,LJKZ0427)
沈阳市重大科技成果转化项目(20-203-5-45)资助。
关键词
齐墩果酸衍生物
结构改造
抗肿瘤
计算机辅助设计
oleanolic acid derivatives
Structural transformation
Antineoplastic
Computer-aided design
