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氟喹诺酮C-3均三唑席夫碱硫乙酸的合成及抗肿瘤活性(X)

张会丽, 李珂, 赵辉, 胡国强, 黄文龙

张会丽, 李珂, 赵辉, 胡国强, 黄文龙. 氟喹诺酮C-3均三唑席夫碱硫乙酸的合成及抗肿瘤活性(X)[J]. 中国药科大学学报, 2017, 48(2): 167-171. DOI: 10.11665/j.issn.1000-5048.20170206
引用本文: 张会丽, 李珂, 赵辉, 胡国强, 黄文龙. 氟喹诺酮C-3均三唑席夫碱硫乙酸的合成及抗肿瘤活性(X)[J]. 中国药科大学学报, 2017, 48(2): 167-171. DOI: 10.11665/j.issn.1000-5048.20170206
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ZHANG Huili, LI Ke, ZHAO Hui, HU Guoqiang, HUANG Wenlong. Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin(X)[J]. Journal of China Pharmaceutical University, 2017, 48(2): 167-171. DOI: 10.11665/j.issn.1000-5048.20170206
Citation: ZHANG Huili, LI Ke, ZHAO Hui, HU Guoqiang, HUANG Wenlong. Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin(X)[J]. Journal of China Pharmaceutical University, 2017, 48(2): 167-171. DOI: 10.11665/j.issn.1000-5048.20170206
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氟喹诺酮C-3均三唑席夫碱硫乙酸的合成及抗肿瘤活性(X)

  • 1.

    郑州工业应用技术学院药学院

  • 2.

    河南大学药学院

  • 3.

    中国药科大学新药研究中心

基金项目: 国家自然科学基金资助项目(No.20872028,No.21072045)

Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin(X)

摘要

    摘要
  • 摘要: 为进一步发现培氟沙星C-3羧基等排体-均三唑的结构优化新方法，用硫乙酸和席夫碱侧链作为其修饰基团，设计合成了12个新的C-3均三唑硫乙酸席夫碱目标化合物( 7a ~ 7l )，其结构经元素分析和光谱数据确证，评价了它们对SMMC-7721、L1210和HL60 3种肿瘤细胞株的体外抗增殖活性。初步药理筛选结果表明，目标化合物的抗肿瘤活性显著高于母体化合物 1 和前体胺 6 ，尤其是苯环含氟原子和硝基的目标化合物( 7j，7l )对SMMC-7721的IC50已达到毫摩尔浓度。实验结果表明，氟喹诺酮C-3羧基的等排体均三唑杂环用席夫碱和硫乙酸这两种功能基侧链修饰有利于提高氟喹诺酮的抗肿瘤活性。
    Abstract: To explore a new strategy for further optimization to the C-3 bioisteric heterocyclic ring of fluoroquinolones, twelve novel fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives( 7a - 7l )were designed and synthesized with both functionalized sulfanylacetic acid and Schiff-base moieties as the modified side-chain for the C-3 bioisosteric s-triazole ring of pefloxacin( 1 ). The structures were characterized by elemental analysis and spectral data, and the in vitro anti-tumor activity of the title compounds against SMMC-7721, L1210 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds possessed more significantly anti-proliferative activity than either the parent 1 or the corresponding amine intermediates( 6 ). In particular, the title compound bearing a fluorine atom( 7j )and compound bearing a nitro group attached to benzene ring( 7l )were comparable to the control doxorubicin against SMMC-7721 cells with an IC50 value of micro-molar concentration, respectively. It suggests that s-triazole ring modified with functional side-chain moieties instead of the C-3 carboxylic group is favorable to the improvement of antitumor activity.
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    • 参考文献(9)
  • [1] Aldred KJ,Schwanz HA,Li G,et al.Activity of quinolone CP-115,955 against bacterial and human type II topoisomerases is mediated by different interactions[J].Biochemistry,2015,54(5):1278-1286.
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    [3] Xu QJ,Hou LL,Wu ZF,et al.Synthesis and antitumor activity of fluoroquinolone C-3 bioisosteres(III):s-triazole-oxadiazole methylsulfide derivatives from pefloxacin[J].J China Pharm Univ(中国药科大学学报),2013,44(6):511-514.
    [4] Sun YS,Xu QJ,Hou LL,et al.Synthesis and antitumor activity of fluoroquinolone C-3 bioisosteres(IV):s-triazole-oxadiazole methylsulfide Mannich-base derivatives[J].J China Pharm Univ(中国药科大学学报),2014,45(1):39-42.
    [5] Xie YS,Gao LZ,Yan Q,et al.Synthesis and antitumor activity of fluoroquinolone C-3 isosteres(VIII):s-triazole sulfide-one thiosemicarbazone derivatives from pefloxacin[J].J China Pharm Univ(中国药科大学学报),2015,46(4):416-420.
    [6] Yan Q,Wu SM,Ni LL,et al.Synthesis and antitumor activity of fluoroquinolone C-3 thiazolo[3,2-b][1,2,4] triazole-substituted pefloxacin derivatives[J].J China Pharm Univ(中国药科大学学报),2015,46(5):548-551.
    [7] Liao ZQ, Dong C, Carlson KE, et al. Triaryl-substituted Schiff bases are high-affinity subtype-selective ligands for the estrogen receptor[J].J Med Chem,2014,57(8):3532-3545.
    [8] Hu GQ,Wu XK,Wang X,et al.Synthesis and antitumor activity of C3 heterocyclic-substituted fluoroquinolone derivatives(I):ciprofloxacin aminothiadiazole Schiff bases[J].Acta Pharm Sin(药学学报),2008,43(11):1112-1115.
    [9] Hu GQ,Hou LL,Wang GQ,et al.Synthesis and antitumor and antibacterial activities of C-3 isosteres I.Norfloxacin C-3 carbonylhydrazone derivatives[J].J China Pharm Univ(中国药科大学学报),2012,43(4):298-301.
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  • 刊出日期:  2017-04-24

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