含1,3,4-噻二唑和吡唑的酰胺衍生物的合成和抗肿瘤活性研究
收稿日期: 2021-02-18
修回日期: 2021-03-30
网络出版日期: 2021-05-14
基金资助
国家自然科学基金(22078072); 广东省基础与应用基础研究基金(2019A1515110346); 茂名市科技计划(2019401); 茂名市科技计划(2020581); 广东石油化工学院博士生启动基金(517152); 广东石油化工学院博士生启动基金(2019rc053); 广东石油化工学院青年创新人才培养基金(517136)
Synthesis and Antitumor Activity of Amide Derivatives Containing 1,3,4-Thiadiazole and Pyrazole Moieties
Received date: 2021-02-18
Revised date: 2021-03-30
Online published: 2021-05-14
Supported by
National Natural Science Foundation of China(22078072); Guangdong Basic and Applied Basic Research Foundation(2019A1515110346); Science and Technology Plan of Maoming(2019401); Science and Technology Plan of Maoming(2020581); Doctor Startup Project of Guangdong University of Petrochemical Technology(517152); Doctor Startup Project of Guangdong University of Petrochemical Technology(2019rc053); Young Creative Talents Training Project of Guangdong University of Petrochemical Technology(517136)
以苯乙酮和草酸二乙酯为原料, 设计并合成了一系列含有1,3,4-噻二唑和吡唑的新型酰胺衍生物A1~A26, 通过1H NMR, 13C NMR, IR, ESI-MS和HRMS等多种手段对其结构进行了表征. 通过噻唑蓝(MTT)方法评估了这些化合物对人肝癌细胞(HepG2)和人胃癌细胞(MGC803)体外抗肿瘤活性的表现. 实验结果表明, 以5-氟尿嘧啶作为阳性对照药物(IC50=0.0787 μmol/mL), 化合物A1 (IC50=0.0695 μmol/mL), A2 (IC50=0.0682 μmol/mL)和A3 (IC50=0.0753 μmol/mL)对HepG2细胞表现出相似的抑制作用. 值得注意的是, 化合物A1对MGC803细胞表现出较强的抑制作用 (IC50=0.0420 μmol/ mL), 远比阳性对照药物5-氟尿嘧啶(IC50=0.0820 μmol/mL)优异.
马姣丽 , 郭鹏虎 , 李静 , 廖新成 , 程辉成 . 含1,3,4-噻二唑和吡唑的酰胺衍生物的合成和抗肿瘤活性研究[J]. 有机化学, 2021 , 41(8) : 3214 -3222 . DOI: 10.6023/cjoc202102030
In this work, a series of newly-synthesized amide derivatives (A1~A26) carrying 1,3,4-thiadiazole and pyrazole moieties were successfully designed and synthesized. In addition, their structures were characterized by multiple techniques including 1H NMR, 13C NMR, IR, ESI-MS and HRMS. Furthermore, based on the antitumor results against human hepatocarcinoma cells (HepG2) and human gastric carcinoma cells (MGC803) via methyl thiazolyl tetrazolium (MTT) method, the in vitro cytotoxic activities of the compounds were evaluated, indicating that compounds A1 (IC50=0.0695 μmol/mL), A2 (IC50=0.0682 μmol/mL) and A3 (IC50=0.0753 μmol/mL) exhibited similar inhibitory effect against HepG2 cells. More importantly, compound A1 displayed superior inhibition performance against MGC803 cells (IC50=0.0420 μmol/mL) compared with that of 5-fluorouracil (IC50=0.0820 μmol/mL).
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