摘要
为寻找新颖的具有靶向治疗作用的抗肿瘤药物,设计并合成了一系列新型含脲基喹唑啉类衍生物,通过1 HNMR、ESI-MS、FTIR对其结构进行了表征,采用CCK-8法对其体外抗肿瘤活性进行了初步评价,对其进行ADME预测,并将其与蛋白质EGFR T790M/L858R进行分子对接。结果表明,衍生物5eⅠ和5eⅡ具有较强的抗肿瘤活性,且衍生物5eⅡ对人肺癌细胞株A549的半数抑制浓度(IC_(50))为(5.13±0.78)μmol·L^(-1),抑制作用优于阳性对照药阿法替尼[IC_(50)=(24.96±0.86)μmol·L^(-1)];ADME预测结果显示衍生物5eⅠ和5eⅡ均符合类药五原则,具有较高的类药性;初步构效关系分析表明将脲基结构引入喹唑啉骨架中可以提高喹唑啉类衍生物的抗肿瘤活性。
In order to search for novel anti-tumor drugs with targeted therapeutic effects,we designed and synthesized a series of novel quinazoline derivatives containing urea groups and characterized their structures by 1 HNMR,ESI-MS,and FTIR.Moreover,we preliminarily evaluated the in vitro anti-tumor activity of derivatives by CCK-8 method.Furthermore,we performed ADME prediction and molecular docking of derivatives with the protein EGFR T790M/L858R.The results show that derivatives 5eⅠand 5eⅡhave high anti-tumor activity,and the IC_(50)value of 5eⅡagainst human lung cancer cell line A549 is(5.13±0.78)μmol·L-1,which is superior to the positive control drug Afatinib[IC_(50)=(24.96±0.86)μmol·L-1].The ADME prediction results show that derivatives 5eⅠand 5eⅡcomply with the Rule of Five and have high drug-likeness.The results of preliminary structure-activity relationship indicate that the introduction of urea groups into quinazoline skeleton can improve the anti-tumor activity of quinazoline derivatives.
作者
李春萌
王亚楠
李举让
曲志卓
蔡志强
李帅
史潇瑀
LI Chunmeng;WANG Yanan;LI Jurang;QU Zhizhuo;CAI Zhiqiang;LI Shuai;SHI Xiaoyu(Liaoning Province Professional and Technical Innovation Center for Fine Chemical Engineering of Aromatics Downstream,School of Petrochemical Engineering,Shenyang University of Technology,Liaoyang 111003,China;Shandong Engineering Research Center of Pharmaceutical Green Intelligent Technology,Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China)
出处
《化学与生物工程》
北大核心
2025年第7期51-57,共7页
Chemistry & Bioengineering
基金
辽宁省自然科学基金项目(20180550016)
辽宁省教育厅科学研究项目(LJGD2020015)。
