注册 English

Design, synthesis and antifungal activity of carbazole derivatives

Shi-Ping Zhu ,  Wen-Ya Wang ,  Kun Fang ,  Zheng-Gang Li ,  Guo-Qiang Dong ,  Zhen-Yuan Miao ,  Jian-Zhong Yao ,  Wan-Nian Zhang ,  Chun-Quan Sheng

downloadPDF
Citation:  Shi-Ping Zhu, Wen-Ya Wang, Kun Fang, Zheng-Gang Li, Guo-Qiang Dong, Zhen-Yuan Miao, Jian-Zhong Yao, Wan-Nian Zhang, Chun-Quan Sheng. Design, synthesis and antifungal activity of carbazole derivatives[J]. Chinese Chemical Letters, 2014, 25(2): 229-233. shu

Design, synthesis and antifungal activity of carbazole derivatives

    • 通讯作者: Wan-Nian Zhang,
    Chun-Quan Sheng,
  • 基金项目:

    This work was supported in part by the National Natural Science Foundation of China (No. 81222044) (No. 81222044)

    the 863 Hi-Tech Program of China (No. 2012AA020302) (No. 2012AA020302)

    Shanghai Rising-Star Program (No. 12QH1402600) (No. 12QH1402600)

    Shanghai Municipal Health Bureau (No. XYQ2011038). (No. XYQ2011038)

摘要: The incidence of invasive fungal infections is increasing rapidly. Clinically available antifungal agents suffer from limited efficacy and severe resistance. There is an urgent need to discover antifungal lead compounds with novel chemical scaffold. On the basis of our previously identified tetrahydrocarbazole antifungal leads, the structure-activity relationship was further explored by modifying the scaffold and the side chains. Several targeted compounds showed potent activity against Candida species. Particularly, compound 13i showed better antifungal activity than the lead compound, which can be used as a good starting point for further optimization.

English

  • 

    1. [1] M.A. Pfaller, D.J. Diekema, Epidemiology of invasive candidiasis: a persistent public health problem, Clin. Microbiol. Rev. 20 (2007) 133-163.[1] M.A. Pfaller, D.J. Diekema, Epidemiology of invasive candidiasis: a persistent public health problem, Clin. Microbiol. Rev. 20 (2007) 133-163.

    2. [2] L. Ostrosky-Zeichner, A. Casadevall, J.N. Galgiani, et al., An insight into the antifungal pipeline: selected new molecules and beyond, Nat. Rev. Drug Discov. 9 (2010) 719-727.[2] L. Ostrosky-Zeichner, A. Casadevall, J.N. Galgiani, et al., An insight into the antifungal pipeline: selected new molecules and beyond, Nat. Rev. Drug Discov. 9 (2010) 719-727.

    3. [3] S.K. Fridkin, W.R. Jarvis, Epidemiology of nosocomial fungal infections, Clin. Microbiol. Rev. 9 (1996) 499-511.[3] S.K. Fridkin, W.R. Jarvis, Epidemiology of nosocomial fungal infections, Clin. Microbiol. Rev. 9 (1996) 499-511.

    4. [4] H.A. Gallis, R.H. Drew, W.W. Pickard, Amphotericin B: 30 years of clinical experience, Rev. Infect. Dis. 12 (1990) 308-329.[4] H.A. Gallis, R.H. Drew, W.W. Pickard, Amphotericin B: 30 years of clinical experience, Rev. Infect. Dis. 12 (1990) 308-329.

    5. [5] D.J. Sheehan, C.A. Hitchcock, C.M. Sibley, Current and emerging azole antifungal agents, Clin. Microbiol. Rev. 12 (1999) 40-79.[5] D.J. Sheehan, C.A. Hitchcock, C.M. Sibley, Current and emerging azole antifungal agents, Clin. Microbiol. Rev. 12 (1999) 40-79.

    6. [6] D.W. Denning, Echinocandins: a new class of antifungal, J. Antimicrob. Chemother. 49 (2002) 889-891.[6] D.W. Denning, Echinocandins: a new class of antifungal, J. Antimicrob. Chemother. 49 (2002) 889-891.

    7. [7] I.A. Casalinuovo, P. Di Francesco, E. Garaci, Fluconazole resistance in Candida albicans: a review of mechanisms, Eur. Rev. Med. Pharmacol. Sci. 8 (2004) 69-77.[7] I.A. Casalinuovo, P. Di Francesco, E. Garaci, Fluconazole resistance in Candida albicans: a review of mechanisms, Eur. Rev. Med. Pharmacol. Sci. 8 (2004) 69-77.

    8. [8] C. Sheng, W. Zhang, New lead structures in antifungal drug discovery, Curr. Med. Chem. 18 (2011) 733-766.[8] C. Sheng, W. Zhang, New lead structures in antifungal drug discovery, Curr. Med. Chem. 18 (2011) 733-766.

    9. [9] W. Wang, G. Dong, J. Gu, et al., Structure-activity relationships of tetrahydrocarbazole derivatives as antifungal lead compounds, Med. Chem. Commun. 4 (2013) 353-362.[9] W. Wang, G. Dong, J. Gu, et al., Structure-activity relationships of tetrahydrocarbazole derivatives as antifungal lead compounds, Med. Chem. Commun. 4 (2013) 353-362.

    10. [10] X. Che, C. Sheng, W. Wang, et al., New azoles with potent antifungal activity: design, synthesis and molecular docking, Eur. J. Med. Chem. 44 (2009) 4218- 4226.[10] X. Che, C. Sheng, W. Wang, et al., New azoles with potent antifungal activity: design, synthesis and molecular docking, Eur. J. Med. Chem. 44 (2009) 4218- 4226.

    11. [11] Z. Jiang, Y. Wang, W. Wang, et al., Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement, Eur. J. Med. Chem. 64C (2013) 16-22.[11] Z. Jiang, Y. Wang, W. Wang, et al., Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement, Eur. J. Med. Chem. 64C (2013) 16-22.

    12. [12] Z. Lv, C. Sheng, Y. Zhang, et al., Synthesis and in vitro antifungal activities of new 3- substituted benzopyrone derivatives, Bioorg. Med. Chem. Lett. 20 (2010) 7106- 7109.[12] Z. Lv, C. Sheng, Y. Zhang, et al., Synthesis and in vitro antifungal activities of new 3- substituted benzopyrone derivatives, Bioorg. Med. Chem. Lett. 20 (2010) 7106- 7109.

    13. [13] C. Sheng, X. Che, W. Wang, et al., Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism, Eur. J. Med. Chem. 46 (2011) 5276- 5282.[13] C. Sheng, X. Che, W. Wang, et al., Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism, Eur. J. Med. Chem. 46 (2011) 5276- 5282.

    14. [14] C. Sheng, X. Che, W. Wang, et al., Structure-based design, synthesis, and antifungal activity of new triazole derivatives, Chem. Biol. Drug. Des. 78 (2011) 309-313.[14] C. Sheng, X. Che, W. Wang, et al., Structure-based design, synthesis, and antifungal activity of new triazole derivatives, Chem. Biol. Drug. Des. 78 (2011) 309-313.

    15. [15] C. Sheng, X. Che, W. Wang, et al., Design and synthesis of antifungal benzoheterocyclic derivatives by scaffold hopping, Eur. J. Med. Chem. 46 (2011) 1706- 1712.[15] C. Sheng, X. Che, W. Wang, et al., Design and synthesis of antifungal benzoheterocyclic derivatives by scaffold hopping, Eur. J. Med. Chem. 46 (2011) 1706- 1712.

    16. [16] C. Sheng, S. Chen, H. Ji, et al., Evolutionary trace analysis of CYP51 family: implication for site-directed mutagenesis and novel antifungal drug design, J. Mol. Model. 16 (2010) 279-284.[16] C. Sheng, S. Chen, H. Ji, et al., Evolutionary trace analysis of CYP51 family: implication for site-directed mutagenesis and novel antifungal drug design, J. Mol. Model. 16 (2010) 279-284.

    17. [17] C. Sheng, H. Xu, W. Wang, et al., Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors, Eur. J. Med. Chem. 45 (2010) 3531-3540.[17] C. Sheng, H. Xu, W. Wang, et al., Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors, Eur. J. Med. Chem. 45 (2010) 3531-3540.

    18. [18] 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.[18] 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.

    19. [19] W. Wang, C. Sheng, X. Che, et al., Discovery of highly potent novel antifungal azoles by structure-based rational design, Bioorg. Med. Chem. Lett. 19 (2009) 5965-5969.[19] W. Wang, C. Sheng, X. Che, et al., Discovery of highly potent novel antifungal azoles by structure-based rational design, Bioorg. Med. Chem. Lett. 19 (2009) 5965-5969.

    20. [20] W. Wang, C. Sheng, X. Che, et al., Design, synthesis, and antifungal activity of novel conformationally restricted triazole derivatives, Arch Pharm. (Weinheim) 342 (2009) 732-739.[20] W. Wang, C. Sheng, X. Che, et al., Design, synthesis, and antifungal activity of novel conformationally restricted triazole derivatives, Arch Pharm. (Weinheim) 342 (2009) 732-739.

    21. [21] W. Wang, S. Wang, Y. Liu, et al., Novel conformationally restricted triazole derivatives with potent antifungal activity, Eur. J. Med. Chem. 45 (2010) 6020- 6026.[21] W. Wang, S. Wang, Y. Liu, et al., Novel conformationally restricted triazole derivatives with potent antifungal activity, Eur. J. Med. Chem. 45 (2010) 6020- 6026.

    22. [22] Y. Xu, C. Sheng, W. Wang, et al., Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives, Bioorg. Med. Chem. Lett. 20 (2010) 2942-2945.[22] Y. Xu, C. Sheng, W. Wang, et al., Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives, Bioorg. Med. Chem. Lett. 20 (2010) 2942-2945.

    23. [23] J. Yao, H. Liu, T. Zhou, et al., Total synthesis and structure-activity relationships of new echinocandin-like antifungal cyclolipohexapeptides, Eur. J. Med. Chem. 50 (2012) 196-208.[23] J. Yao, H. Liu, T. Zhou, et al., Total synthesis and structure-activity relationships of new echinocandin-like antifungal cyclolipohexapeptides, Eur. J. Med. Chem. 50 (2012) 196-208.

    24. [24] M. Desroses, K. Wieckowski, M. Stevens, et al., A microwave-assisted, propylphosphonic anhydride (T3P.(R).) mediated one-pot Fischer indole synthesis, Tetrahedron Lett. 52 (2011) 4417-4420.[24] M. Desroses, K. Wieckowski, M. Stevens, et al., A microwave-assisted, propylphosphonic anhydride (T3P.(R).) mediated one-pot Fischer indole synthesis, Tetrahedron Lett. 52 (2011) 4417-4420.

    25. [25] H. Gan, H. Liu, Y. Li, et al., Fabrication of polydiacetylene nanowires by associated self-polymerization and self-assembly processes for efficient field emission properties, J. Am. Chem. Soc. 127 (2005) 12452-12453.[25] H. Gan, H. Liu, Y. Li, et al., Fabrication of polydiacetylene nanowires by associated self-polymerization and self-assembly processes for efficient field emission properties, J. Am. Chem. Soc. 127 (2005) 12452-12453.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1411
  • HTML全文浏览量:  45
文章相关
  • 收稿日期:  2013-08-29
  • 网络出版日期:  2013-10-09
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