欧前胡素酯类衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity evaluation of imperatorin ester derivatives

作　　者：陈贵芬 张敏杰 陈娅芳 於祥 杨武德 CHEN Gui-fen;ZHANG Min-jie;CHEN Ya-fang;YU Xiang;YANG Wu-de(College of pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025

出　　处：《化学研究与应用》2023年第12期2982-2988,共7页Chemical Research and Application

基　　金：国家自然科学基金项目(82260833)资助;贵州省自然科学基金项目(黔科合基础[2020]1Y070)资助。

摘　　要：天然产物欧前胡素具有广泛的抗肿瘤活性,应用前景巨大。本论文以欧前胡素为先导化合物,通过氧化、还原、酯化等反应设计合成了13个欧前胡素酯类衍生物,并经^(1)H NMR、^(13)C NMR、HRMS进行结构确证。通过MTT法测定了目标化合物在200μmol·L^(-1)下对宫颈癌细胞HeLa、结肠癌细胞HCT116和肝癌细胞HePG2三种肿瘤细胞的体外抗肿瘤活性。结果显示目标化合物3g对肝癌细胞HePG2表现出显著的抑制活性,超过了原料欧前胡素,与阳性对照药索拉非尼和5-氟尿嘧啶相当。分子对接结果显示3g可以和抗凋亡蛋白Mcl-1通过多种作用力稳定结合。Imperatorin is a small molecule nature compound,and exhibits a wide range of antitumor activity and great application prospect.In this work,thirteen imperatorin-based ester derivatives were synthesized via oxidation,reduction and esterification.Their structures were also confirmed by ^(1)H NMR,^(13)C NMR and HRMS.The antitumor activities of these derivatives against cervical canc-er cells HeLa,colon cancer cells HCT116 and liver cancer cells HePG2 in vitro were determined by MTT assay at 200μmol·L^(-1).The bioassay results showed that compound 3g had a significant inhibitory activity against liver cancer cells HePG2,higher than that of imperatorin,and was equivalent to those of positive control drug sorafenib and fluorouracil.Molecular docking study suggested that 3g could stably bind with amino acid residues of Mcl-1,the anti-apoptotic protein,through varies effects.

关 键 词：欧前胡素 抗凋亡蛋白 抗肿瘤活性 分子对接 

分 类 号：O626[理学—有机化学]