目的 设计合成N-(4-甲基-3-((4-(吡啶-3-基)嘧啶-2-基)氨基)苯基)氨基脲衍生物,并对其体外抗肿瘤活性进行研究。方法 N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)-2-嘧啶胺为起始原料,经还原、酰化、肼解及与异氰酸酯的反应,合成了目标化合物,采用MTT法研究了目标化合物对人乳腺癌细胞(MCF-7)和人肝癌细胞(HepG2)的体外抗肿瘤活性。结果 合成了13个新化合物,其结构经1H-NMR,13C-NMR 和HRMS表征。体外生物活性测试结果显示,大多数化合物具有一定的体外抗肿瘤活性,其中化合物5l活性最优,其对MCF-7、HepG2细胞的半数抑制浓度(IC50)分别为9.1、10.45 μmol·L-1,对正常肝细胞LO2的半数抑制浓度(IC50)为53 μmol·L-1,并且诱导细胞周期G2-M期阻滞。结论 该系列化合物具有较好的抗肿瘤活性,具有进一步研究的意义。
Abstract
OBJECTIVE To design and synthesize N-(4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) phenyl) hydrazinecarboxamides and investigate their in vitro antitumor activities. METHODS The target compounds were synthesized from N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidine amine through reduction, acylation, hydrazinolysis, and reaction with isocyanates. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human breast (MCF-7) and human hepatoma cell (HepG2) cancer cell lines by MTT assay. RESULTS Thirteen novel compounds were obtained, and their structures were characterized by 1H-NMR, 13C-NMR and HRMS. In vitro bioassay indicated that most compounds showed antitumor activity. Compound 5l displayed the most potential anticancer activity against these cancer cell lines with IC50 value of 9.15 and 10.45 μmol·L-1 respectively, without obvious toxic effects on normal liver cells with IC50 value of 53 μmol·L-1, and it also induced G2/M cell cycle arrest. CONCULUSION The series of compunds show preferable antitumor activities, which are worthy of further study.
关键词
氨基脲 /
吡啶联嘧啶 /
抗肿瘤活性
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Key words
semicarbazide /
pyridylpyrimidine /
antitumor activity
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中图分类号：
R914.5
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基金
国家级大学生创新创业训练计划项目资助;金华市科技局公益项目资助(2019-4-005,2020-4-088);宁波市自然科学基金项目资助(202003N4160)
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