熊果酸-三氮唑衍生物的合成及抗肿瘤活性研究  

Synthesis and anti-tumor activity of ursolic acid-triazole derivatives

作　　者：蒯振彧 孟艳秋 KUAI Zhen-yu;MENG Yan-qiu(Department of Pharmacy Teaching and Research,Maanshan Technical College,Maanshan 243031,China;Department of Pharmaceutical Engineering,Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]马鞍山职业技术学院药学教研室,安徽马鞍山243031 [2]沈阳化工大学制药与生物工程学院,辽宁沈阳110142

出　　处：《药学学报》2025年第1期172-178,共7页Acta Pharmaceutica Sinica

基　　金：安徽省高校自然科学研究项目(2024AH051790,KJ2021A1340);国家自然科学基金资助项目(82473787)。

摘　　要：以熊果酸为母体,对其C-3和C-28位进行结构修饰,引入1,2,3-三氮唑,合成了10个新型熊果酸衍生物,结构经MS、1H NMR和13C NMR确证。通过MTT法,选用高表达人癌细胞(乳腺癌MCF-7和胃癌SGC-7901细胞)对化合物进行初步体外抗肿瘤活性筛选,结果表明,所有化合物对MCF-7和SGC-7901肿瘤细胞的抑制活性均明显高于熊果酸。其中化合物II4对MCF-7和SGC-7901细胞具有较强的抗肿瘤作用,活性与阳性对照药尼洛替尼相当,分子对接也显示其与c-Kit具有较高的结合能力,值得进一步研究。Ten ursolic acid derivatives were designed from the lead compound ursolic acid by introducing 1,2,3-triazole at C-3 and C-28.The target compounds were synthesized and characterized by'H NMR and I°C NMR.MTT assay was used to study the antitumor activity of these compounds in human cancer cells with high expression(MCF-7 and SGC-7901).The results showed that the antitumor activity of all compounds on MCF-7 and SGC-7901 tumor cells was significantly higher than that of ursolic acid.The compound II4 exhibited significant antitumor activity which was equivalent to the positive control drug nilotinib,molecular docking showed that the compound Il,have high binding ability with c-Kit,which deserves further research.

关 键 词：熊果酸 分子对接 C-KIT 结构修饰 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]