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2012 , Vol. 32 >Issue 05: 922 - 929

DOI: https://doi.org/10.6023/cjoc1107241

研究论文

氟康唑衍生物的设计合成及体外抗真菌活性研究

  • 王楠 ,
  • 李文娟 ,
  • 张雷 ,
  • 高一军 ,
  • 冀春梅 ,
  • 陈营 ,
  • 柴晓云 ,
  • 孙海军 ,
  • 毕毅 ,
  • 吴秋业 ,
  • 孟庆国
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  • a 烟台大学药学院 烟台 264005;
    b 潍坊市人民医院 潍坊 261041;
    c 第二军医大学药学院 上海 200433

收稿日期: 2011-07-24

  修回日期: 2011-11-11

  网络出版日期: 2011-12-02

基金资助

国家自然科学基金(No. 81072534)资助项目.

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Design, Synthesis and in vitro Antifungal Activities of Fluconazole Derivatives

  • Wang Nan ,
  • Li Wenjuan ,
  • Zhang Lei ,
  • Gao Yijun ,
  • Ji Chunmei ,
  • Chen Ying ,
  • Chai Xiaoyun ,
  • Sun Haijun ,
  • Bi Yi ,
  • Wu Qiuye ,
  • Meng Qingguo
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  • a School of Pharmacy, Yantai University, Yantai 264005;
    b Weifang People1’s Hospital, Weifang 261041;
    c School of Pharmacy, Second Military Medical University, Shanghai 200433

Received date: 2011-07-24

  Revised date: 2011-11-11

  Online published: 2011-12-02

Supported by

Project supported by the National Natural Science Foundation of China (No. 81072534).

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摘要

为了寻找活性更好的抗真菌化合物, 基于已有的计算机辅助药物设计结果, 保留氟康唑母体结构必需药效团,设计、合成了22 个含对甲酚和胸腺嘧啶的氟康唑新衍生物. 目标化合物的结构经1H NMR、元素分析和ESI-MS 确证,初步体外抗真菌活性试验结果表明, 化合物5l 对7 种真菌都表现出了较好的抗真菌活性(烟曲霉菌除外), 化合物5a～5e, 5g, 5h, 7a 和7b 对不同真菌表现出了一定的抗真菌活性. 炔丙基取代氨基侧链结构的引入有利于提高该类目标化合物体外抗真菌活性, 值得进一步深入研究.

关键词： 氟康唑; 衍生物; 合成; 设计; 体外抗真菌活性

本文引用格式

王楠 , 李文娟 , 张雷 , 高一军 , 冀春梅 , 陈营 , 柴晓云 , 孙海军 , 毕毅 , 吴秋业 , 孟庆国 . 氟康唑衍生物的设计合成及体外抗真菌活性研究[J]. 有机化学, 2012 , 32(05) : 922 -929 . DOI: 10.6023/cjoc1107241

Abstract

In search of more effective antifungal agents, twenty-two new fluconazole derivatives containing 4-methyl phenol and thymine have been designed and synthesized based on the previous results of computer-aided drug design. All the derivatives retain the essential pharmacophore of fluconazole. Their structures are elucidated by 1H NMR, elemental analysis and ESI-MS. Preliminary in vitro antifungal activities bioassay showed that compound 5l exhibits better in vitro antifungal activities against eight fungi except Aspergillus fumigatus (7544) than fluconazole, compounds 5a～5e, 5g, 5h, 7a and 7b show only moderate in vitro antifungal activities against different fungus. The introduction of propargyl group to nitrogen atom can enhance in vitro antifungal activities of this type derivative and it is worth of further research.

Key words： fluconazole; derivative; synthesis; design; in vitro antifungal activity

参考文献

[1] Hossain, M. A.; Ghannoum, M. A. Expert Opin. Invest. Drugs2000, 9, 1797.  

[2] Wexler, D.; Courtney, R.; Richards, W.; Banfield, C.; Lim, J.;Laughlin, M. Eur. J. Pharm. Sci. 2004, 21, 645.

[3] Stevens, D. J. Cancer. 1995, 32, 1.

[4] Odds, F. C. J. Antimicrob. Chemther. 1993, 31, 463.  

[5] Kauffman, C.; Carver, P. Drugs 1997, 53, 539.  

[6] Li, D.; Chen, B.-Y. Chin. J. Tuberc. Respir. Dis. 2009, 32, 235 (inChinese).(李冬, 陈佰义, 中华结核和呼吸杂志, 2009, 32, 235.)

[7] Pfaller, M. A.; Messer, S. A.; Hollis, R. J.; Jones, R. N.; Doern, G.V.; Brandt, M. E.; Hajjeh, R. A. Antimicrob. Agents Chemtherapy.1998, 42: 3242.  

[8] Law, D.; Moore, C. B.; Denning, D. W. Antimicrob. Agents Chemther.1997, 41, 2310.

[9] Fung-Tomc, J. C.; Huczko, E.; Minassian, B. Bonner, D. P. Antimicrob.Agents Chemther. 1998, 42, 313.

[10] Schell, W. A.; De Almeida, G. M. D.; Dodge, R. K.; Okonogi, K.J.; Perfect, J. R. Antimicrob. Agents Chemther. 1998, 42, 2630.

[11] Robert, A.; Fromtling, J.; Castaner, L. Drugs Fut. 1999, 24, 30.  

[12] Chai, X.-Y. M.S. Thesis, Second Military Medical University,Shanghai, 2009 (in Chinese).(柴晓云, 硕士论文, 第二军医大学, 上海, 2009.)

[13] Patrick, J. F.; Neil, J. G.; Rachel, F.; Alan, H.; Tom, B. Nucleic AcidsRes. 1996, 24, 3357.  

[14] National Committee for Clinical Laboratory Standards, ReferenceMethod for Broth Dilution Antifungal Susceptibility Testing ofYeasts Approved standard, Document M27-A2, National Committeefor Clinical Laboratory Standards, Wayne, PA, 2002.
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