N-羟基-5-(3-取代脲)-1H-吲哚-2-酰胺衍生物的合成及其抗肿瘤活性研究

郭叡霖, 盛含晶, 赵胜贤, 严晓阳,胡鸿雨

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (15) : 1234-1242.

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中国药学杂志
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中国药学杂志 ›› 2020, Vol. 55 ›› Issue (15) : 1234-1242. DOI: 10.11669/cpj.2020.15.002
论著

N-羟基-5-(3-取代脲)-1H-吲哚-2-酰胺衍生物的合成及其抗肿瘤活性研究

  • 郭叡霖1, 盛含晶1, 赵胜贤2, 严晓阳1,胡鸿雨1*
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Synthesis and Antitumor Activities of N-hydroxy-5-(3-substituted ureido)-1H-indole-2-carboxamide Derivatives

  • GUO Rui-lin1, SHENG Han-jing1, ZHAO Sheng-xian2, YAN Xiao-yang1, HU Hong-yu1*
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摘要

目的 设计合成N-羟基-5-(3-取代脲)-1H-吲哚-2-酰胺衍生物,并对其体外抗肿瘤活性进行研究。方法 以对硝基苯肼和丙酮酸乙酯为起始原料采用缩合、Fischer吲哚合成法等方法合成了一系列新型的N-羟基-5-(3-取代脲)-1H-吲哚-2-酰胺衍生物(7a~7n),并通过1H-NMR、13C-NMR和HRMS对所有目标化合物进行了结构鉴定。采用溴化噻唑蓝四氮唑比色(MTT)法考察了目标化合物对宫颈癌细胞(Hela)、乳腺癌细胞(MCF-7)及人肝癌细胞(HepG-2)等细胞系的细胞毒进行了活性测试。结果 设计合成的目标化合物对所选癌细胞的增值活性具有一定抑制作用,其中化合物 7j、7l和7m对Hela的抑制活性优于顺铂。结论 该系列化合物对Hela、MCF-7和HepG-2具有较好的抑制作用,具有进一步研究的意义。

Abstract

OBJECTIVE To design and synthesize N-hydroxy-5-(3-substituted urea)-1H-indole-2-amide derivatives and investigate their anti-tumor activity in vitro. METHODS A series of new N-hydroxy-5-(3-substituted ureido)-1H-indole-2-carboxamide derivatives (7a-7n)were designed and prepared from p-nitrophenylhydrazine and ethyl pyruvate. Their antitumor activities against Hela (breast cancer) lines, cervical cancer cell (MCF7) and human hepatoma cell lines (HepG2) were evaluated by methyl thiazolyl (MTT) method. RESULTS Target compounds indicated certain antitumor activities,especially compound 7h showed the strongest cytotoxicity to Hela cells with a half inhibition concentration (IC50) of 7.31 μmol·L-1. CONCLUSION The series of compounds show preferable antitumor activities, which are worthy of further study.

关键词

吲哚 / 酰胺衍生物 / 合成 / 抑制活性

Key words

indole / carboxamide derivatives / synthesis / inhibitory activity

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郭叡霖, 盛含晶, 赵胜贤, 严晓阳,胡鸿雨. N-羟基-5-(3-取代脲)-1H-吲哚-2-酰胺衍生物的合成及其抗肿瘤活性研究[J]. 中国药学杂志, 2020, 55(15): 1234-1242 https://doi.org/10.11669/cpj.2020.15.002
GUO Rui-lin, SHENG Han-jing, ZHAO Sheng-xian, YAN Xiao-yang, HU Hong-yu. Synthesis and Antitumor Activities of N-hydroxy-5-(3-substituted ureido)-1H-indole-2-carboxamide Derivatives[J]. Chinese Pharmaceutical Journal, 2020, 55(15): 1234-1242 https://doi.org/10.11669/cpj.2020.15.002
中图分类号： R914.5   

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基金

浙江省教育厅一般课题资助(Y201941989);金华市科技计划项目资助(2019-4-005,2020-4-088);浙江大学生新苗人才计划资助(2019R404045)
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