Design, synthesis and antifungal activities of novel pyrrole- and pyrazole-substituted coumarin derivatives

Abstract

We synthesized a series of novel pyrrole- and pyrazole-substituted coumarin derivatives and evaluated their antifungal activity against six phytopathogenic fungi in vitro. The primary assay results demonstrated that some designed compounds displayed potent activities. Among them, compounds 5g, 6a, 6b, 6c, 6d and 6h exhibited more effective control than Osthole against Cucumber anthrax and Alternaria leaf spot. Furthermore, compound 5g displayed stronger antifungal activity against Rhizoctorzia solani (EC50 = 15.4 µg/mL) than positive control Osthole (EC50 = 67.2 µg/mL).

Graphical abstract

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Scheme 1

References

  1. 1.

    Hu YQ, Xu Z, Zhang S, Wu X, Ding JW, Lv ZS, Feng LS (2017) Recent development of coumarin-containing derivatives and their anti-tubercular activity. Eur J Med Chem 136:122–130. https://doi.org/10.1016/j.ejmech.2017.05.004

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Emami S, Dadashpour S (2015) Current developments of coumarin-based anti-cancer agents in medicinal chemistry. Eur J Med Chem 102:611–630. https://doi.org/10.1016/j.ejmech.2015.08.033

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Vogl S, Zehl M, Picker P, Urban E, Wawrosch C, Reznicek G, Saukel J, Kopp B (2011) Identification and quantification of coumarins in Peucedanum ostruthium (L.) Koch by HPLC-DAD and HPLC-DAD-MS. J Agric Food Chem 59:4371–4377. https://doi.org/10.1021/jf104772x

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    lyer D, Patil UK (2014) Evaluation of antihyperlipidemic and antitumor activities of isolated coumarins from Salvadora indica. Pharm Biol 52:78–85. https://doi.org/10.3109/13880209.2013.815633

    CAS  Article  Google Scholar 

  5. 5.

    Shah MR, Shamim A, White LS, Bertino MF, Mesaik MA, Soomro S (2014) The anti-inflammatory properties of Au-scopoletin nanoconjugates. New J Chem 38:5566–5572. https://doi.org/10.1039/C4NJ00792A

    CAS  Article  Google Scholar 

  6. 6.

    Liu W, Wu J, Wang SJ, Kong WS, Qin YH, Yang GY, Chen YK (2014) A new coumarin from roots and stems of flue-cured tobacco and its anti-tobacco mosaic virus activity. Asian J Chem 26:2820–2822. https://doi.org/10.14233/ajchem.2014.15807

    CAS  Article  Google Scholar 

  7. 7.

    Domagala A, Jarosz T, Lapkowski M (2015) Living on pyrrolic foundations-Advances in natural and artificial bioactive pyrrole derivatives. Eur J Med Chem 100:176–187. https://doi.org/10.1016/j.ejmech.2015.06.009

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Gholap SS (2016) Pyrrole: an emerging scaffold for construction of valuable therapeutic agents. Eur J Med Chem 110:13–31. https://doi.org/10.1016/j.ejmech.2015.12.017

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Ahmad S, Alam O, Javed Naim M, Shaquiquzzaman M, Mumtaz Alam M, Iqbal M (2018) Pyrrole: an insight into recent pharmacological advances with structure activity relationship. Eur J Med Chem 157:527–561. https://doi.org/10.1016/j.ejmech.2018.08.002

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Küçükgüzel ŞG, Şenkardeş S (2015) Recent advances in bioactive pyrazoles. Eur J Med Chem 97:786–815. https://doi.org/10.1016/j.ejmech.2014.11.059

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Khan MF, Alam MM, Verma G, Akhtar W, Akhter M, Shaquiquzzaman M (2016) The therapeutic voyage of pyrazole and its analogs: a review. Eur J Med Chem 120:170–201. https://doi.org/10.1016/j.ejmech.2016.04.077

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Zhu XF, van Pée KH, Naismith JH (2010) The ternary complex of PrnB (the second enzyme in the pyrrolnitrin biosynthesis pathway), tryptophan, and cyanide yields new mechanistic insights into the indolamine dioxygenase superfamily. J Biol Chem 285:21126–21133. https://doi.org/10.1074/jbc.M110.120485

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Santos AFLOM, Ribeiro da Silva MAV (2010) Experimental and computational thermochemistry of 1-phenylpyrrole and 1-(4-methylphenyl)pyrrole. J Chem Thermodynamics 42:734–741. https://doi.org/10.1016/j.jct.2010.01.009

    CAS  Article  Google Scholar 

  14. 14.

    Bennett JW, Bentley R (2000) Seeing red: the story of prodigiosin. Adv Appl Microbiol 47:1–32. https://doi.org/10.1016/S0065-2164(00)47000-0

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Williamson NR, Flineran PC, Leeper FJ, Salmond GPC (2006) The biosynthesis and regulation of bacterial prodiginines. Nat Rev Microbiol 4:887–899. https://doi.org/10.1038/nrmicro1531

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Williamson NR, Fineran PC, Gristwood T, Chawrai SR, Leeper FJ, Salmond GPC (2007) Anticancer and immunosuppressive properties of bacterial prodiginines. Future Microbiol 2:605–618. https://doi.org/10.2217/17460913.2.6.605

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Hassan GS, Abou-Seri SM, Kamel G, Ali MM (2014) Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: design, synthesis and evaluation as potential anti-inflammatory agents. Eur J Med Chem 76:482–493. https://doi.org/10.1016/j.ejmech.2014.02.033

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Sun HY, Ji FQ (2012) A molecular dynamics investigation on crizotinib resistance mechanism of C1156Y mutation in ALK. Biochem Biophys Res Comm 423:319–324. https://doi.org/10.1016/j.bbrc.2012.05.120

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Brune K (1997) The early history of non-opioid analgesics. Acute Pain 1:33–40. https://doi.org/10.1016/S1366-0071(97)80033-2

    CAS  Article  Google Scholar 

  20. 20.

    Zhang MZ, Zhang RR, Yin WZ, Yu X, Zhang YL, Liu P, Gu YC, Zhang WH (2016) Microwave-assisted Synthesis and antifungal activity of coumarin[8,7-e] [1, 3]oxazine derivatives. Mol Divers 20:611–618. https://doi.org/10.1007/s11030-016-9662-2

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Zhang RR, Liu J, Zhang Y, Hou MQ, Zhang MZ, Zhou F, Zhang WH (2016) Microwave-assisted synthesis and antifungal activity of novel coumarin derivatives: pyrano[3,2-c]chromene-2,5-diones. Eur J Med Chem 116:76–83. https://doi.org/10.1016/j.ejmech.2016.03.069

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Zhang MZ, Zhang RR, Wang JQ, Yu X, Zhang YL, Wang QQ, Zhang WH (2016) Microwave-assisted synthesis and antifungal activity of novel fused Osthole derivatives. Eur J Med Chem 124:10–16. https://doi.org/10.1016/j.ejmech.2016.08.012

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Zhang MZ, Zhang Y, Wang JQ, Zhang WH (2016) Design, synthesis and antifungal activity of coumarin ring-opening derivatives. Molecules 21:1387. https://doi.org/10.3390/molecules21101387

    CAS  Article  PubMed Central  Google Scholar 

  24. 24.

    Yu X, Wen Y, Liang CG, Liu J, Ding YB, Zhang WH (2017) Design, synthesis and antifungal activity of psoralen derivatives. Molecules 22:1672. https://doi.org/10.3390/molecules22101672

    CAS  Article  PubMed Central  Google Scholar 

  25. 25.

    Yu X, Teng P, Zhang YL, Xu ZJ, Zhang MZ, Zhang WH (2018) Design, synthesis and antifungal activity evaluation of coumarin-3-carboxamide derivatives. Fitoterapia 127:387–395. https://doi.org/10.1016/j.fitote.2018.03.013

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Huang M, Xie SS, Jiang N, Lan JS, Kong LY, Wang XB (2015) Multifunctional coumarin derivatives: monoamine oxidase B (MAO-B) inhibition, anti-β-amyloid (Aβ) aggregation and metal chelation properties against Alzheimer’s disease. Bioorg Med Chem Lett 25:508–513. https://doi.org/10.1016/j.bmcl.2014.12.034

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Kathuria A, Priya N, Chand K, Singh P, Gupta A, Jalal S, Gupta S, Raj HG, Sharma SK (2012) Substrate specificity of acetoxy derivatives of coumarins and quinolones towards calreticulin mediated transacetylation: investigations on antiplatelet function. Bioorg Med Chem 20:1624–1638. https://doi.org/10.1016/j.bmc.2011.11.016

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Liu YF, Chen ZY, Ng TB, Zhang J, Zhou MG, Song FP, Lu F, Liu YZ (2007) Bacisubin, an antifungal protein with ribonuclease and hemagglutinating activities from Bacillus subtilis strain B-916. Peptides 28:553–559. https://doi.org/10.1016/j.peptides.2006.10.009

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Program of National Key R&D Program of China (2018YFD0200103) and the Fundamental Research Funds for the Central Universities (KYTZ 201604) for partially funding this work.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Wei-Hua Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 3444 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, S., Liang, C., Sun, Y. et al. Design, synthesis and antifungal activities of novel pyrrole- and pyrazole-substituted coumarin derivatives. Mol Divers 23, 915–925 (2019). https://doi.org/10.1007/s11030-019-09920-z

Download citation

Keywords

  • Aminocoumarin derivatives
  • Nitrogen-containing
  • Synthesis
  • Antifungal activity