含噻吩并[3,2-d]嘧啶的查尔酮类化合物的合成及其抗增殖活性
Synthesis and antiproliferative activity of chalcone derivatives bearing thieno[3,2-d]pyrimidine moiety
黄婷 1孙安霞 2崔益铭 2张浩阳2
作者信息
- 1. 安康学院 化学化工学院,陕西 安康 725000;陕西省富硒食品质量监督检验中心,陕西 安康 725000
- 2. 安康学院 化学化工学院,陕西 安康 725000
- 折叠
摘要
运用药物分子片段原理及拼合原理,设计并以70.1%～83.9%的收率合成了10个含噻吩并[3,2-d]嘧啶的查尔酮类衍生物,并对该类化合物的体外抗肿瘤细胞增殖活性进行初步研究.通过1HNMR、13CNMR和HRMS(ESI)确证了目标化合物的结构.以人肺腺癌细胞株A549、人肝癌细胞株HepG2和人前列腺癌细胞株PC-3 3种肿瘤细胞为测试细胞株,采用四甲基偶氮唑盐(MTT)法评价了目标化合物的抗增殖活性.结果表明,10个化合物对3种肿瘤细胞株均具有很好的抑制活性.其中,3-{4-[4-(2-氯噻吩并[3,2-d]嘧啶-4-基)哌嗪-1-羰基]苯基}-1-(3,4-二甲氧基苯基)丙基-2-烯-1-酮(Ⅶh)活性突出,对A549、HepG2和PC-3 3种肿瘤细胞株的半抑制浓度(IC50)分别为(0.87±0.05)、(2.43±0.16)和(2.02±0.10)μmol/L,优于阳性对照药索拉非尼.
Abstract
Ten chalcone derivatives bearing thieno[3,2-d]pyrimidine moiety with yield ranging from 70.1%～83.9%were successfully designed and synthesized based on the principle of drug molecular fragment and splicing,with their structures confirmed by 1HNMR,13CNMR and HRMS(ESI).The compounds were further evaluated for their in vitro antitumor activity via methylthiazoletetrazolium(MTT)assay using human lung adenocarcinoma(A549)cell lines,human liver cancer(HepG2)cell lines and human prostate cancer(PC-3)cell lines as model lines.The results showed that all target compounds showed excellent antiproliferative activities against all tested cancer cell lines.Among them,3-{4-[4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)piperazine-1-carbonyl]phenyl}-1-(3,4-dimethoxyphenyl)propyl-2-ene-1-one exhibited remarkable inhibitory activity against A549,HepG2 and PC-3 cell lines with half maximal inhibitory concentration(IC50)of(0.87±0.05),(2.43±0.16)and(2.02±0.10)μmol/L,respectively,which were more potent than the positive control sorafenib.
关键词
药物分子设计/查尔酮/噻吩并[3,2-d]嘧啶/合成/抗增殖活性/医药与日化原料Key words
drug molecular design/chalcone/thieno[3,2-d]pyrimidine/synthesis/antiproliferative activity/drug and cosmetic materials引用本文复制引用
基金项目
陕西省创新型人才支持计划项目(陕人64015号)
陕西省研究生教育教学改革重点课题(陕教合18019)
陕西省重点实验室项目(19JS003)
陕西省青年创新团队项目(21JP002)
安康市秦创原"科学家+工程师"队伍建设项目(2022AKKXJ-03)
国家级大学生创新创业项目(202211397023)
陕西省富硒食品质量监督检验中心(2023AYPT05)
出版年
2024
NETL
NSTL
维普
万方数据