[1]李 珂),张会丽),闻 婧),等.氟喹诺酮C-3噁二唑硫乙酰腙的合成及抗肿瘤活性测定*[J].郑州大学学报(医学版),2017,(01):28-33.[doi:10.13705/j.issn.1671-6825.2017.01.008]
 LI Ke),ZHANG Huili),WEN Jing),et al.Synthesis and antitumor activity detection of fluoroquinolone C-3 oxadiazole sulfanylacetylhydrazones[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(01):28-33.[doi:10.13705/j.issn.1671-6825.2017.01.008]
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氟喹诺酮C-3噁二唑硫乙酰腙的合成及抗肿瘤活性测定*()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2017年01期
页码:
28-33
栏目:
论著
出版日期:
2017-01-15

文章信息/Info

Title:
Synthesis and antitumor activity detection of fluoroquinolone C-3 oxadiazole sulfanylacetylhydrazones
作者:
李 珂1)张会丽1)闻 婧2)胡国强2)#黄文龙3)
1)郑州工业应用技术学院药学院 郑州 451150;
2)河南大学药学院 河南开封 475001;
3)中国药科大学新药研究中心 南京 210009
Author(s):
LI Ke1) ZHANG Huili1) WEN Jing2) HU Guoqiang2) HUANG Wenlong3)
1)School of Pharmacy, Zhengzhou University of Industrial Technology, Zhengzhou 451150;
2)School of Pharmacy, Henan University, Kaifeng, Henan 475001;
3)Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009
关键词:
氟喹诺酮 噁二唑 酰腙 生物电子等排体 抗肿瘤活性
Keywords:
fluoroquinolone oxadiazole acylhydrazone bioisostere antitumor activity
分类号:
R979.1
DOI:
10.13705/j.issn.1671-6825.2017.01.008
摘要:
目的:发现氟喹诺酮由抗菌活性转化为抗肿瘤活性的有效结构修饰策略。方法:用噁二唑杂环作为环丙沙星C-3羧基的生物电子等排体,硫乙酰腙为其功能修饰侧链,合成10个新氟喹诺酮C-3噁二唑硫乙酰腙目标化合物,其结构经元素分析和光谱数据确证,并评价其体外对SMMC-7721、L1210和HL60等3种癌细胞的抗增殖作用。结果:目标物的抗肿瘤活性高于母体化合物,尤其是苯环含有氟原子和硝基的化合物,其抗肿瘤作用与对照阿霉素相当。结论:噁二唑杂环可用于氟喹诺酮C-3羧基的等排体,被功能基侧链修饰有利于提高抗肿瘤活性。
Abstract:
Aim: To discover an efficient strategy for a conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones.Methods: Ten novel fluoroquinolone C-3 oxadiazole sulfanylacetylhydrazone derivatives were designed and synthesized with an oxadiazole ring as the C-3 bioisostere modified by a functionalized sulfanylacetylhydrazone side-chain from ciprofloxacin, respectively. The structures of the title compounds were characterized by elemental analysis and spectral data, and the in vitro antitumor activity against SMMC-7721, L1210 and HL60 cell lines was evaluated by MTT assay.Results: The title compounds demonstrated more antiproliferative activity than the parent. In particular, compounds bearing a fluorine atom or nitro group attached to benzene ring were comparable to the control doxorubicin.Conclusion: An azole modified with functionalized side-chain as the bioisosteric replacement of the C-3 carboxylic group is favorable to improvement of antitumor activity.

参考文献/References:

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[3] 尚慧杰,高留州,谢玉锁,等.N-甲基环丙沙星酰腙的合成及抗肿瘤活性[J].郑州大学学报(医学版),2015,50(5):597
[4] YOU QD,LI ZY,HUANG CH,et al.Discovery of a novel series of quinolone and naphthyridine derivatives as potential topoisomerase Ⅰ inhibitors by scaffold modification[J].J Med Chem,2009,52(18):5649
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 SHANG Huijie),GAO Liuzhou),XIE Yusuo),et al.Synthesis and antitumor activity of N-methyl ciprofloxacin acylhydrazone[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(01):597.
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备注/Memo

备注/Memo:
*国家自然科学基金面上资助项目 20872028,21072045
#通信作者,男,1964 年3 月生,博士,教授,研究方向:新药分子的设计与合成,E-mail:hgqxy@sina.com
更新日期/Last Update: 2017-01-20