Display options
Cite
Clementino LDC, Fernandes GFS, Prokopczyk IM, et al. Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity. PLoS One. 2021;16(11):e0259008doi: 10.1371/journal.pone.0259008.
Clementino, L. D. C., Fernandes, G. F. S., Prokopczyk, I. M., Laurindo, W. C., Toyama, D., Motta, B. P., Baviera, A. M., Henrique-Silva, F., Santos, J. L. D., & Graminha, M. A. S. (2021). Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity. PloS one, 16(11), e0259008. https://doi.org/10.1371/journal.pone.0259008
Clementino, Leandro da Costa, et al. "Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity." PloS one vol. 16,11 (2021): e0259008. doi: https://doi.org/10.1371/journal.pone.0259008
Clementino LDC, Fernandes GFS, Prokopczyk IM, Laurindo WC, Toyama D, Motta BP, Baviera AM, Henrique-Silva F, Santos JLD, Graminha MAS. Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity. PLoS One. 2021 Nov 01;16(11):e0259008. doi: 10.1371/journal.pone.0259008. eCollection 2021. PMID: 34723989; PMCID: PMC8559926.
Copy Download .nbib Format: NLM
Share it on

PLoS One. 2021 Nov 01;16(11):e0259008. doi: 10.1371/journal.pone.0259008. eCollection 2021.

Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.

PloS one

Leandro da Costa Clementino, Guilherme Felipe Santos Fernandes, Igor Muccilo Prokopczyk, Wilquer Castro Laurindo, Danyelle Toyama, Bruno Pereira Motta, Amanda Martins Baviera, Flávio Henrique-Silva, Jean Leandro Dos Santos, Marcia A S Graminha

Affiliations

  1. São Paulo State University (UNESP), Institute of Chemistry, Araraquara, Brazil.
  2. São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, Brazil.
  3. Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, Brazil.

PMID: 34723989 PMCID: PMC8559926 DOI: 10.1371/journal.pone.0259008

Abstract

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

Conflict of interest statement

The authors have declared that no competing interests exist.

References

  1. PLoS Negl Trop Dis. 2019 Mar 25;13(3):e0007235 - PubMed
  2. Biomed Pharmacother. 2015 Oct;75:93-9 - PubMed
  3. Nature. 1970 Aug 15;227(5259):680-5 - PubMed
  4. Antimicrob Agents Chemother. 2018 Sep 24;62(10): - PubMed
  5. Bioorg Med Chem. 1999 Apr;7(4):639-44 - PubMed
  6. Eur J Med Chem. 2012 Dec;58:613-23 - PubMed
  7. Front Cell Infect Microbiol. 2019 Oct 29;9:353 - PubMed
  8. J Parasit Dis. 2010 Apr;34(1):1-13 - PubMed
  9. J Med Chem. 2017 Oct 26;60(20):8647-8660 - PubMed
  10. J Biotechnol. 2002 Oct 9;99(1):51-62 - PubMed
  11. J Med Chem. 2012 Sep 13;55(17):7583-92 - PubMed
  12. Curr Protein Pept Sci. 2001 Jun;2(2):137-53 - PubMed
  13. Clin Microbiol Rev. 2018 Aug 29;31(4): - PubMed
  14. Biochem J. 2000 Apr 15;347(Pt 2):383-8 - PubMed
  15. Bioorg Med Chem. 2008 Sep 1;16(17):7900-7 - PubMed
  16. Infect Immun. 1991 Mar;59(3):1074-8 - PubMed
  17. Front Cell Infect Microbiol. 2019 Jun 28;9:229 - PubMed
  18. Eur J Med Chem. 2018 Aug 5;156:587-597 - PubMed
  19. Antimicrob Agents Chemother. 2014 Aug;58(8):4837-47 - PubMed
  20. J Immunol. 2004 Sep 1;173(5):3297-304 - PubMed
  21. J Cell Sci. 1995 Oct;108 ( Pt 10):3219-31 - PubMed
  22. Exp Parasitol. 2015 Sep;156:42-8 - PubMed
  23. Nat Rev Drug Discov. 2015 Nov;14(11):751-8 - PubMed
  24. Biomed Pharmacother. 2017 Nov;95:536-547 - PubMed
  25. Methods Enzymol. 1981;80 Pt C:535-61 - PubMed
  26. Drug Dev Res. 2020 Apr 6;: - PubMed
  27. Sci Rep. 2017 Mar 03;7:42717 - PubMed
  28. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6008-13 - PubMed
  29. Curr Drug Targets. 2014;15(12):1121-31 - PubMed
  30. J Biol Chem. 1998 Sep 25;273(39):25112-6 - PubMed
  31. Bioorg Chem. 2020 Jul;100:103948 - PubMed
  32. PLoS One. 2012;7(5):e35671 - PubMed
  33. Eur J Med Chem. 2013 Jan;59:64-74 - PubMed
  34. Eur J Med Chem. 2018 Jun 25;154:341-353 - PubMed
  35. J Med Chem. 2011 Aug 25;54(16):5811-9 - PubMed
  36. J Enzyme Inhib Med Chem. 2013 Aug;28(4):661-70 - PubMed
  37. Biochim Biophys Acta. 2001 Feb 9;1545(1-2):357-66 - PubMed
  38. J Comput Aided Mol Des. 2010 Jun;24(6-7):591-604 - PubMed
  39. Antimicrob Agents Chemother. 2007 May;51(5):1700-7 - PubMed
  40. Eur J Med Chem. 2009 Dec;44(12):5055-65 - PubMed
  41. PLoS Negl Trop Dis. 2018 Aug 23;12(8):e0005850 - PubMed
  42. Chem Biol Drug Des. 2018 Sep;92(3):1585-1596 - PubMed
  43. ChemMedChem. 2010 Oct 4;5(10):1734-48 - PubMed
  44. Microbes Infect. 2012 Dec;14(15):1377-89 - PubMed
  45. Eur J Med Chem. 2016 Nov 10;123:523-531 - PubMed
  46. Bioorg Med Chem. 2020 Nov 15;28(22):115743 - PubMed
  47. PLoS Negl Trop Dis. 2010 May 11;4(5):e676 - PubMed
  48. Bioorg Med Chem. 2009 Jan 15;17(2):641-52 - PubMed
  49. PLoS One. 2013 Oct 16;8(10):e77460 - PubMed
  50. Free Radic Biol Med. 2011 Jul 15;51(2):337-51 - PubMed
  51. Biochim Biophys Acta. 2004 Dec 1;1703(1):69-77 - PubMed
  52. Lancet. 2018 Sep 15;392(10151):951-970 - PubMed
  53. PLoS Negl Trop Dis. 2018 Aug 23;12(8):e0006512 - PubMed
  54. Expert Opin Pharmacother. 2015 Feb;16(2):237-52 - PubMed
  55. Front Cell Dev Biol. 2020 Jun 10;8:396 - PubMed
  56. J Med Chem. 2004 Mar 25;47(7):1750-9 - PubMed
  57. Toxicon. 2016 Jun 1;115:49-54 - PubMed
  58. J Biol Chem. 1993 Mar 25;268(9):6115-8 - PubMed
  59. Mol Microbiol. 1992 Jul;6(14):1925-32 - PubMed

Publication Types