注册 English

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

Hui Tang ,  Can-Hui Zheng ,  Xiao-Hui Ren ,  Jia Liu ,  Na Liu ,  Jia-Guo Lv ,  Ju Zhu ,  You-Jun Zhou

downloadPDF
Citation:  Hui Tang, Can-Hui Zheng, Xiao-Hui Ren, Jia Liu, Na Liu, Jia-Guo Lv, Ju Zhu, You-Jun Zhou. Synthesis and biological evaluation of novel triazole derivatives as antifungal agents[J]. Chinese Chemical Letters, 2013, 24(3): 219-222. shu

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

    • 通讯作者: Can-Hui Zheng,
    You-Jun Zhou,
摘要: A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro. The results showed that compounds 6A and 6B exhibited good antifungal activity. Compound 6A8 showed the strongest antifungal activity, which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole. In particular, the antifungal activity of compound 6A8 against Candida albicans and Candida krusei (MIC80 both at 0.00097 mg/mL) was 515 and 64 times that of Fluconazole, respectively. The structure-activity relationships of the synthesized compounds were discussed, and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.

English

  • 

    1. [1] B.J. Kullberg, A.M. Oude Lashof, Epidemiology of opportunistic invasive mycoses, Eur. J. Med. Res. 7 (2002) 183-191.[1] B.J. Kullberg, A.M. Oude Lashof, Epidemiology of opportunistic invasive mycoses, Eur. J. Med. Res. 7 (2002) 183-191.

    2. [2] D.A. Enoch, H.A. Ludlam, N.M. Brown, Invasive fungal infections: a review of epidemiology and management options, J. Med. Microbiol. 55 (2006) 809-818.[2] D.A. Enoch, H.A. Ludlam, N.M. Brown, Invasive fungal infections: a review of epidemiology and management options, J. Med. Microbiol. 55 (2006) 809-818.

    3. [3] E. Rodriguez-Fernandez, J.L. Manzano, J.J. Benito, et al., Thiourea, triazole and thiadiazine compounds and their metal complexes as antifungal agents, J. Inorg. Biochem. 99 (2005) 1558-1572.[3] E. Rodriguez-Fernandez, J.L. Manzano, J.J. Benito, et al., Thiourea, triazole and thiadiazine compounds and their metal complexes as antifungal agents, J. Inorg. Biochem. 99 (2005) 1558-1572.

    4. [4] H. Hof, Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine? Drug Resist. Updat. 11 (2008) 25-31.[4] H. Hof, Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine? Drug Resist. Updat. 11 (2008) 25-31.

    5. [5] P. Eggimann, J. Garbino, D. Pittet, Management of Candida species infections in critically ill patients, Lancet Infect. Dis. 3 (2003) 772-785.[5] P. Eggimann, J. Garbino, D. Pittet, Management of Candida species infections in critically ill patients, Lancet Infect. Dis. 3 (2003) 772-785.

    6. [6] J. Peman, E. Canton, A. Espinel-Ingroff, Antifungal drug resistance mechanisms, Expert. Rev. Anti. Infect. Ther. 7 (2009) 453-460.[6] J. Peman, E. Canton, A. Espinel-Ingroff, Antifungal drug resistance mechanisms, Expert. Rev. Anti. Infect. Ther. 7 (2009) 453-460.

    7. [7] A.K. Gupta, E. Tomas, New antifungal agents, Dermatol. Clin. 21 (2003) 565-576.[7] A.K. Gupta, E. Tomas, New antifungal agents, Dermatol. Clin. 21 (2003) 565-576.

    8. [8] G.R. Thompson Ⅲ, J. Cadena, T.F. Patterson, Overview of antifungal agents, Clin. Chest Med. 30 (2009) 203-215.[8] G.R. Thompson Ⅲ, J. Cadena, T.F. Patterson, Overview of antifungal agents, Clin. Chest Med. 30 (2009) 203-215.

    9. [9] H. Ji, W. Zhang, Y. Zhou, et al., A three-dimensional model of lanosterol 14alphademethylase of Candida albicans and its interaction with azole antifungals, J. Med. Chem. 43 (2000) 2493-2505.[9] H. Ji, W. Zhang, Y. Zhou, et al., A three-dimensional model of lanosterol 14alphademethylase of Candida albicans and its interaction with azole antifungals, J. Med. Chem. 43 (2000) 2493-2505.

    10. [10] Z. Guan, X. Chai, S. Yu, et al., Synthesis, molecular docking, and biological evaluation of novel triazole derivatives as antifungal agents, Chem. Biol. Drug. Des. 76 (2010) 496-504.[10] Z. Guan, X. Chai, S. Yu, et al., Synthesis, molecular docking, and biological evaluation of novel triazole derivatives as antifungal agents, Chem. Biol. Drug. Des. 76 (2010) 496-504.

    11. [11] C. Sheng, W. Zhang, H. Ji, et al., Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and molecular docking, J. Med. Chem. 49 (2006) 2512-2525.[11] C. Sheng, W. Zhang, H. Ji, et al., Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and molecular docking, J. Med. Chem. 49 (2006) 2512-2525.

    12. [12] National Committee for Clinical Laboratory Standards, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts Approved standard, Document M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, 2002.[12] National Committee for Clinical Laboratory Standards, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts Approved standard, Document M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, 2002.

    13. [13] B. Yao, H. Ji, Y. Cao, et al., Synthesis and antifungal activities of novel 2-aminotetralin derivatives, J. Med. Chem. 50 (2007) 5293-5300.[13] B. Yao, H. Ji, Y. Cao, et al., Synthesis and antifungal activities of novel 2-aminotetralin derivatives, J. Med. Chem. 50 (2007) 5293-5300.

    14. [14] X. Chai, J. Zhang, S. Yu, et al., Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols, Bioorg. Med. Chem. Lett. 19 (2009) 1811-1814.[14] X. Chai, J. Zhang, S. Yu, et al., Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted benzylamino-2-propanols, Bioorg. Med. Chem. Lett. 19 (2009) 1811-1814.

    15. [15] X. Chai, J. Zhang, H. Hu, et al., synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14alpha-demethylase, Eur. J. Med. Chem. 44 (2009) 1913-1920.[15] X. Chai, J. Zhang, H. Hu, et al., synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14alpha-demethylase, Eur. J. Med. Chem. 44 (2009) 1913-1920.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1025
  • HTML全文浏览量:  25
文章相关
  • 收稿日期:  2012-10-26
  • 网络出版日期:  2012-12-17
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net