Skip to main content
SpringerLink
Log in

Design, synthesis, and biological evaluation of novel 5-bromo derivatives of indole phytoalexins

  • Original Paper
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

The increasing diversity of small molecule libraries is a major source for the discovery of new drug candidates. In terms of this trend, we report the synthesis of five series 5-bromosubstituted derivatives of indole phytoalexins Types A–E using a straightforward synthetic approach. Novel compounds were screened in vitro for antiproliferative/cytotoxic activity against seven human cancer cell lines by MTT assay. Evaluation of their antiproliferative potency showed that the activity of some analogues was better or comparable to that of cisplatin and at the same time the toxicity of these compounds on 3T3 cells was lower than that of cisplatin. We found that all 5-bromosubstituted analogues of indole phytoalexins Types A–E exhibited lower or approximately the same activities as previously studied corrensponding non-brominated compounds.

Graphic abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pedras MSC, Abdoli A (2017) RSC Adv 7:23633

    Article  Google Scholar 

  2. Takasugi M, Katsui N, Shirata AJ (1986) Chem Soc Chem Commun 1077

  3. Takasugi M, Monde K, Katsui N, Shirata A (1987) Chem Lett 1631

  4. Gross D, Porzel A, Schmidt J (1994) Z Naturforsch C 49:281

    Article  CAS  Google Scholar 

  5. Monde K, Takasugi M, Shirata A (1995) Phytochemistry 39:581

    Article  CAS  Google Scholar 

  6. Storck M, Sacristan MD (1995) Z Naturforsch 50c:15

  7. Mezencev R, Galizzi M, Kutschy P, Docampo R (2009) Exp Parasitol 122:66

    Article  CAS  Google Scholar 

  8. Kristofikova Z, Gazova Z, Siposova K, Bartos A, Ricny J, Kotoucova J, Sirova J, Ripova D (2014) Neurochem Res 39:1502

    Article  CAS  Google Scholar 

  9. Mehta RG, Naithani R, Huma L, Hawthorne M, Moriarty RM, McCormick DL, Steele VE, Kopelovich L (2008) Curr Med Chem 15:2785

    Article  CAS  Google Scholar 

  10. Higdon JV, Delage B, Williams DE, Dashwood RH (2007) Pharmacol Res 55:224

    Article  CAS  Google Scholar 

  11. Mezencev R, Mojžiš J, Pilátová M, Kutschy P, Čurillová Z (2004) Int J Canc Prev 1:105

    CAS  Google Scholar 

  12. Pilátová M, Šarišský M, Kutschy P, Miroššay A, Mezencev R, Čurillová Z, Suchý M, Monde K, Miroššay L, Mojžiš J (2005) Leukemia Res 29:415

    Article  Google Scholar 

  13. Chripkova M, Drutovic D, Pilatova M, Mikes J, Budovska M, Vaskova J, Broggini M, Mirossay L, Mojzis J (2014) Toxicol In Vitro 28:909

    Article  CAS  Google Scholar 

  14. Mezencev R, Mojžiš J, Pilátová M, Kutschy P, Čurillová Z (2007) Effects of phytoalexins on the growth of cancer cells. In: Columbus F (ed) Trends in cancer prevention research. Nova Science Publishers, New York, p 81

    Google Scholar 

  15. Kutschy P, Mezencev R (2008) Indole phytoalexins from brassicaceae: synthesis and anticancer activity. In: Attanasi OA, Spinelli D (eds) Targets in heterocyclic systems—chemistry and properties, vol 12. Italian Society of Chemistry, Urbino, Italy, p 120

    Google Scholar 

  16. Chripkova M, Zigo F, Mojzis J (2016) Molecules 21:1626

    Article  Google Scholar 

  17. Domico LM, Zeevalk GD, Bernard LP, Cooper KR (2006) Neurotoxicology 27:816

    Article  CAS  Google Scholar 

  18. Izutani Y, Yogosawa S, Sowa Y, Sakai T (2012) Int J Oncol 40:816

    CAS  PubMed  Google Scholar 

  19. Banerjee T, Duhadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ (2008) Oncogene 27:2851

    Article  CAS  Google Scholar 

  20. Kim SM, Oh EY, Lee JH, Nam D, Lee SG, Lee J, Kim SH, Shim BS, Ahn KS (2015) Phytother Res 29:1828

    Article  CAS  Google Scholar 

  21. Lee JH, Kim C, Sethi G, Ahn KS (2015) Oncotarget 6:6386

    Article  Google Scholar 

  22. Bakar-Ates F, Ozkan E (2019) Phytother Res 33:397

    Article  CAS  Google Scholar 

  23. Han BH, Yoon JJ, Choi ES, Jeong DH, Lee YJ, Kang DG, Lee HS (2017) Mol Med Rep 16:6890

    Article  Google Scholar 

  24. Kang B, Kim CY, Hwang J, Suh HJ, Choi HS (2019) Phytother Res 33:1426

    Article  CAS  Google Scholar 

  25. Budovská M, Pilatová M, Varinská L, Mojžiš J, Mezencev R (2013) Bioorg Med Chem 21:6623

    Article  Google Scholar 

  26. Budovská M, Baláž M, Mezencev R, Tischlerová V, Zigová M, Mojžiš J (2018) J Fluorine Chem 216:24

    Article  Google Scholar 

  27. Budovská M, Tischlerová V, Mojžiš J, Kozlov O, Gondová T (2020) Monatsh Chem 151:63

    Article  Google Scholar 

  28. Kello M, Drutovic D, Chripková M, Pilatová M, Budovská M, Kuliková L, Urdzík P, Mojžiš J (2014) Molecules 19:10877

    Article  Google Scholar 

  29. Budovská M, Tischlerová V, Mojžiš J, Harvanová M, Kozlov O, Gondová T, Tomášková N (2017) Tetrahedron 73:6356

    Article  Google Scholar 

  30. Mezencev R, Kutschy P, Salayova A, Curillova Z, Mojzis J, Pilatova M, McDonald J (2008) Chemotherapy 54:372

    Article  CAS  Google Scholar 

  31. Kutschy P, Salayová A, Čurillová Z, Kožár T, Mezencev R, Mojžiš J, Pilátová M, Balentová E, Pazdera P, Sabol M, Zburová M (2009) Bioorg Med Chem 17:3698

    Article  CAS  Google Scholar 

  32. Tischlerová V, Kello M, Budovská M, Mojžiš J (2017) World J Gastroenterol 23:4341

    Article  Google Scholar 

  33. Solárová Z, Kello M, Varinská L, Budovská M, Solár P (2017) Biomed Pharmacother 85:463

    Article  Google Scholar 

  34. Zhong X, Chen N, Xu J (2018) New J Chem 42:13549

    Article  CAS  Google Scholar 

  35. Pauletti PM, Cintra LS, Braguine CG, da Silva Filho AA, e Silva MLA, Cunha WR, Januário AH (2010) Mar Drugs 8:1526

  36. Di Pucchio T, Danese S, De Cristofaro R, Rutella S (2010) Expert Opin Ther Pat 20:229

    Article  Google Scholar 

  37. Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH (2007) Cancer Res 67:792

    Article  CAS  Google Scholar 

  38. Očenášová L, Kutschy P, Gonda J, Pilátová M, Gönciová G, Mojžiš J, Pazdera P (2016) Chem Pap 70:635

    Google Scholar 

  39. Pedras MSC, Suchý M, Ahiahonu PWK (2006) Org Biomol Chem 4:691

    Article  CAS  Google Scholar 

  40. Topls JGJ (1972) Med Chem 15:1006

    Article  Google Scholar 

  41. Mosmann T (1983) J Immunol Methods 65:55

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The present study was supported in part by the Grant Agency of Ministry of the Education, Science, Research and Sport of the Slovak Republic (VEGA 1/0753/17) and the Slovak Research and Development Agency under the contract No. APVV-16-0446. Moreover, this publication is the result of the project implementation: “Medicínsky univerzitný vedecký park v Košiciach (MediPark, Košice—Fáza II.)”, kód ITMS2014 + 313011D103 supported by the Operational Programme Research & Innovation, funded by the ERDF.

Author information

Authors and Affiliations

  1. Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University in Košice, Moyzesova 11, 040 01, Košice, Slovak Republic

    Mariana Budovská & Ivana Selešová

  2. Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, SNP 1, 040 11, Košice, Slovak Republic

    Viera Tischlerová, Radka Michalková & Ján Mojžiš

Authors
  1. Mariana Budovská
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivana Selešová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Viera Tischlerová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Radka Michalková
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ján Mojžiš
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariana Budovská.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Budovská, M., Selešová, I., Tischlerová, V. et al. Design, synthesis, and biological evaluation of novel 5-bromo derivatives of indole phytoalexins. Monatsh Chem 151, 1737–1758 (2020). https://doi.org/10.1007/s00706-020-02693-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-020-02693-4

Keywords

Search

Navigation