桦木醇-28-吲哚酯衍生物的设计合成及抗癌活性研究  

Design,Synthesis,and Anticancer Activity of Betulin-28-indole Ester Derivatives

作　　者：潘思文 张英博 张萌[2] 郭晓珊 卜明 王佳丰 PAN Si-wen;ZHANG Ying-bo;ZHANG Meng;GUO Xiao-shan;BU Ming;WANG Jia-feng(College of Pathology,Qiqihar Medical University,Qiqihar 161006,China;Animal Laboratory Center,Qiqihar Medical University,Qiqihar 161006,China;College of Nursing,Qiqihar Medical University,Qiqihar 161006,China;College of Pharmacy,Qiqihar Medical University,Qiqihar 161006,China)

机构地区：[1]齐齐哈尔医学院病理学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院实验动物管理中心,黑龙江齐齐哈尔161006 [3]齐齐哈尔医学院护理学院,黑龙江齐齐哈尔161006 [4]齐齐哈尔医学院药学院,黑龙江齐齐哈尔161006

出　　处：《化学试剂》2025年第2期94-101,共8页Chemical Reagents

基　　金：黑龙江省省属本科高校基本科研业务费科技项目(2022-KYYWF-0787)。

摘　　要：为了寻找结构新颖、抗癌活性显著的先导化合物,以桦木醇为原料,设计并合成了一系列桦木醇-28-吲哚酯衍生物,并对合成产物进行了抗增殖活性测试、靶点预测和分子对接研究。结果表明,所有衍生物对3种癌细胞的抑制作用均优于桦木醇。其中,桦木醇-28-((6-氟)吲哚-3-)乙酸酯对3种癌细胞均表现出了低微摩尔级别的抗增殖活性(IC 50<10.00μmol/L),其对A549细胞的作用最强(IC 50=7.25μmol/L),是桦木醇的4.15倍。作用机制研究表明,上述化合物可能通过抑制PI3K-Akt通路发挥抗癌作用。总之,该化合物是一种具有良好抗癌活性的先导化合物,对其进一步的结构修饰和药理研究具有重要的意义。In order to find lead compounds with novel structure and remarkable anticancer activity,a series of Betulin-28-indole ester derivatives were designed and synthesized from Betulin.The synthesized products were tested for anticancer activities,and target prediction and molecular docking studies were carried out in this project.The results showed that the inhibitory effects of all derivatives on the three cancer cells were better than that of Betulin.Among them,Betulin-28-((6-fluoro)indole-3-)acetate displayed low micromolar anti-proliferative activity against three cancer cells(IC 50<10.00μmol/L),and its effect was the strongest against A549 cells(IC 50=7.25μmol/L),which was 4.15 times that of Betulin.The mechanism study has shown that the above compound may play an anticancer role by inhibiting the PI3K-Akt pathway.In conclusion,this compound is a promising lead compound with excellent anticancer activity,and further structural modification and pharmacological studies on it hold great significance.

关 键 词：桦木醇 吲哚 结构修饰 抗癌活性 PI3K-Akt通路 

分 类 号：R914[医药卫生—药物化学]