[6/6]倍半萜类衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity of[6/6]sesquiterpene derivatives

作　　者：马永菲 陈晖 李硕 杨秀娟 智怡菱 段国建 MA Yongfei;CHEN Hui;LI Shuo;YANG Xiujuan;ZHI Yiling;DUAN Guojian(College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou,Gansu,730000P.R.China)

机构地区：[1]甘肃中医药大学药学院,甘肃兰州730000

出　　处：《华西药学杂志》2024年第6期633-638,共6页West China Journal of Pharmaceutical Sciences

基　　金：甘肃省科技计划资助项目(24JRRA883);甘肃省自然科学基金项目(23JRRA1716);甘肃省高等学校创新基金项目(2021A-079);甘肃省中医药管理局(GZKP-2022-37);2024年甘肃省高校大学生就业创新提升工程项目(202402)。

摘　　要：目的合成[6/6]倍半萜类衍生物并测试其抗肿瘤活性。方法以5-氯-1-戊炔和3-甲基-2-环己烯-1-酮为原料,经7步反应,构建了[6/6]倍半萜骨架,再利用酯化反应,得到5个[6/6]倍半萜类衍生物。采用CCK-8法测定目标化合物对人宫颈癌Hela细胞、人非小细胞肺癌A549细胞、人膀胱癌5637细胞的抑制作用。结果目标化合物对上述3种肿瘤细胞均有抑制作用。其中,化合物Ⅱ对Hela细胞和5637细胞,化合物Ⅰc对A549细胞具有显著的抑制作用,半数抑制浓度分别为17.28、16.99、14.72μg·mL^(-1)。结论制备了目标化合物并进行构效关系分析,可为[6/6]倍半萜类抗肿瘤药物的结构优化提供参考。OBJECTIVE To synthesize[6/6]sesquiterpenoid derivatives and test their antitumor activity.METHODS The[6/6]sesquiterpene skeleton was constructed by a 7 step reaction using 5-chloro-1-pentyne and 3-methyl-2-cyclohexen-1-one as raw materials,and then using esterification reaction,five[6/6]sesquiterpene derivatives were obtained.The inhibitory effects of the target compounds on human cervical cancer Hela cells,human non-small cell lung cancer A549 cells,and human bladder cancer 5637 cells were determined using CCK-8 assay.RESUITS The target compounds showed different degrees of inhibitory effects on the above three types of tumor cells.Among them,compoundⅡshowed significant inhibitory effects on Hela cells and 5637 cells,and compoundⅠc on A549 cells,with IC_(50)of 17.28,16.99 and 14.72μg·mL^(-1),respectively.CONCLUSION The analysis of the conformational relationship results of the target compounds synthesized can provide a reference basis for the structural optimization of the[6/6]sesquiterpene antitumor drugs.

关 键 词：[6/6]倍半萜 衍生物 合成 结构骨架 抗肿瘤活性 ADMET预测 酯化 人膀胱癌细胞 

分 类 号：R914[医药卫生—药物化学]