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Metal complex derivatives of bis(pyrazol-1-yl)methane ligands: synthesis, characterization and anti-Trypanosoma cruzi activity

  • Daniela Fonseca
  • Carolina Páez
  • Laura Ibarra
  • Paola García-Huertas
  • Mario A. Macías
  • Omar Triana-Chávez
  • John J. Hurtado
Article

Abstract

In this work, the synthesis and characterization of seven complexes (1–7) was performed with Zn(II), Cu(II), Co(II) and Ni(II) transition metals and ligands derived from bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) and bis(3,5-dimethyl-4-nitro-1H-pyrazolyl)methane (L). The complexes were obtained in high yields, isolated as air-stable solids and characterized by physicochemical and spectroscopic methods. The structures of L and complex 1 were determined by single-crystal X-ray diffraction analysis. The complexes and their respective ligands were evaluated against epimastigotes of Trypanosoma cruzi strains. An increase in the activity of the complexes was observed compared to the free ligands. Greater activities were found for Co(II) complexes than for Cu(II), Ni(II) and Zn(II) complexes. Additionally, complexes 3 and 9 had little effect on erythrocytes, indicating that they are non-toxic. The results obtained in mitochondrial membrane potential analyses suggest a possible mechanism by which complex 3 has a trypanocidal effect through the induction of oxidative stress. The results could provide an interesting contribution to the further design of active complexes against T. cruzi.

Graphical abstract

Synthesis and structural characterization of new complexes with zinc(II), copper(II), cobalt(II) and nickel(II) transition metals derived from bis(pyrazol-1-yl)methane ligands. The cobalt(II) complexes have high activity against epimastigotes from Trypanosoma cruzi strains and are not toxic.

Notes

Acknowledgements

Thanks to the Department of Chemistry and the School of Science of the Universidad de los Andes for financial support. O. Triana acknowledges the Universidad de Antioquia, Estrategia de sostenibilidad UdeA. We thank the reviewers and editor for their useful comments.

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary data

CCDC 1586067 and 1586068 contain supplementary crystallographic data for L and 1, respectively. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html or the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.

Supplementary material

11243_2018_277_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1776 kb)

References

  1. 1.
    Steverding D (2014) The history of Chagas disease. Parasites Vectors 7:1–8.  https://doi.org/10.1186/1756-3305-7-317 CrossRefGoogle Scholar
  2. 2.
    Silva JJN, Osakabe AL, Pavanelli WR et al (2007) In vitro and in vivo antiproliferative and trypanocidal activities of ruthenium NO donors. Br J Pharmacol 152:112–121.  https://doi.org/10.1038/sj.bjp.0707363 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Maya JD, Cassels BK, Iturriaga-Vásquez P et al (2007) Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comput Biochem Physiol A Mol Integr Physiol 146:601–620.  https://doi.org/10.1016/j.cbpa.2006.03.004 CrossRefGoogle Scholar
  4. 4.
    Gutteridge WE (1976) Chemotherapy of Chagas’ disease. Trans R Soc Trop Med Hyg 70:123–124.  https://doi.org/10.1016/0035-9203(76)90169-3 CrossRefPubMedGoogle Scholar
  5. 5.
    Castillo KF, Bello-Vieda NJ, Nuñez-Dallos NG et al (2016) Metal complex derivatives of azole: a study on their synthesis, characterization, and antibacterial and antifungal activities. J Braz Chem Soc 27:2334–2347.  https://doi.org/10.5935/0103-5053.20160130 CrossRefGoogle Scholar
  6. 6.
    Biot C, Castro W, Botté CY, Navarro M (2012) The therapeutic potential of metal-based antimalarial agents: implications for the mechanism of action. Dalt Trans 41:6335.  https://doi.org/10.1039/c2dt12247b CrossRefGoogle Scholar
  7. 7.
    Murcia R, Leal S, Roa M et al (2018) Development of antibacterial and antifungal triazole chromium(III) and cobalt(II) complexes: synthesis and biological activity evaluations. Molecules 23:2013.  https://doi.org/10.3390/molecules23082013 CrossRefGoogle Scholar
  8. 8.
    Bello-Vieda NJ, Pastrana HF, Garavito MF et al (2018) Antibacterial activities of azole complexes combined with silver nanoparticles. Molecules 23:1–17.  https://doi.org/10.3390/molecules23020361 CrossRefGoogle Scholar
  9. 9.
    Hurtado J, Ibarra L, Yepes D et al (2017) Synthesis, crystal structure, catalytic and anti-Trypanosoma cruzi activity of a new chromium(III) complex containing bis(3,5-dimethylpyrazol-1-yl)methane. J Mol Struct 1146:365–372.  https://doi.org/10.1016/j.molstruc.2017.06.014 CrossRefGoogle Scholar
  10. 10.
    Boni A, Pampaloni G, Peloso R et al (2006) Synthesis of copper(I) bis(3,5-dimethylpyrazolyl)methane olefin complexes and their reactivity towards carbon monoxide. J Organomet Chem 691:5614–5621.  https://doi.org/10.1016/j.jorganchem.2006.09.006 CrossRefGoogle Scholar
  11. 11.
    Wang JX, Zhu ZR, Bai FY et al (2015) Molecular design and the optimum synthetic route of the compounds with multi-pyrazole and its derivatives and the potential application in antibacterial agents. Polyhedron 99:59–70.  https://doi.org/10.1016/j.poly.2015.06.020 CrossRefGoogle Scholar
  12. 12.
    Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr Sect C Struct Chem 71:3–8.  https://doi.org/10.1107/S2053229614024218 CrossRefGoogle Scholar
  13. 13.
    Spek AL (2015) PLATON SQUEEZE: a tool for the calculation of the disordered solvent contribution to the calculated structure factors. Acta Crystallogr Sect C Struct Chem 71:9–18.  https://doi.org/10.1107/S2053229614024929 CrossRefGoogle Scholar
  14. 14.
    Park NG, Silphaduang U, Moon HS et al (2011) Structure–activity relationships of piscidin 4, a piscine antimicrobial peptide. Biochemistry 50:3288–3299.  https://doi.org/10.1021/bi101395j CrossRefPubMedGoogle Scholar
  15. 15.
    Navarro-Ranninger MC, Alvarez-Valdés A, Camazón MJ, Masaguer JR (1987) Complexes of copper(II) with substituted benzylideneamines. Inorg Chim Acta 132:7–10.  https://doi.org/10.1016/S0020-1693(00)83982-1 CrossRefGoogle Scholar
  16. 16.
    Parashar RK, Sharma RC, Kumar A, Mohan G (1988) Stability studies in relation to IR data of some schiff base complexes of transition metals and their biological and pharmacological studies. Inorg Chim Acta 151:201–208.  https://doi.org/10.1016/S0020-1693(00)83468-4 CrossRefGoogle Scholar
  17. 17.
    Tarafder MT, Jin KT, Crouse KA et al (2002) Coordination chemistry and bioactivity of Ni2+, Cu2+, Cd2+ and Zn2+ complexes containing bidentate Schiff bases derived from S-benzyldithiocarbazate and the X-ray crystal structure of bis[S-benzyl-β-N-(5-methyl-2-furylmethylene)dithiocarbazato]cadmium(II). Polyhedron 21:2547–2554.  https://doi.org/10.1016/S0277-5387(02)01188-9 CrossRefGoogle Scholar
  18. 18.
    Long DA (2004) Infrared and Raman characteristic group frequencies. Tables and chartsGeorge Socrates John Wiley and Sons, Ltd, Chichester, Third Edition, 2001. Price £135. J Raman Spectrosc 35:905–905.  https://doi.org/10.1002/jrs.1238 CrossRefGoogle Scholar
  19. 19.
    Robinson K, Gibbs GV, Ribbe PH (1971) Quadratic elongation: a quantitative measure of distortion in coordination polyhedra. Science 172:567–570.  https://doi.org/10.1126/science.172.3983.567 CrossRefPubMedGoogle Scholar
  20. 20.
    Cremer D, Pople JA (1975) A General definition of ring puckering coordinates. J Am Chem Soc 97:1354–1358.  https://doi.org/10.1021/ja00839a011 CrossRefGoogle Scholar
  21. 21.
    Sandoval-Rojas AP, Ibarra L, Cortés MT et al (2017) Synthesis and characterization of copper(II) complexes containing acetate and N, N-donor ligands, and their electrochemical behavior in dopamine detection. J Electroanal Chem 805:60–67.  https://doi.org/10.1016/j.jelechem.2017.10.018 CrossRefGoogle Scholar
  22. 22.
    Rueda-Espinosa J, Torres JF, Gauthier CV et al (2017) Copper(II) complexes with tridentate bis(pyrazolylmethyl)pyridine ligands: synthesis, X-ray crystal structures and ϵ-caprolactone polymerization. ChemistrySelect 2:9815–9821.  https://doi.org/10.1002/slct.201701820 CrossRefGoogle Scholar
  23. 23.
    Brewster L, Barbour P, Grundhausex FJ (2000) Possible roles for zinc in destruction of Trypanosoma cruzi by toxic oxygen metabolites produced by mononuclear phagocytes. 61:111–112.  https://doi.org/10.1007/978-1-4613-0553-8_10 Google Scholar
  24. 24.
    de Carvalho LP, de Melo EJT (2017) Life and death of Trypanosoma cruzi in presence of metals. Biometals 30:955–974.  https://doi.org/10.1007/s10534-017-0064-4 CrossRefPubMedGoogle Scholar
  25. 25.
    Eide DJ (2006) Zinc transporters and the cellular trafficking of zinc. Biochim Biophys Acta Mol Cell Res 1763:711–722.  https://doi.org/10.1016/j.bbamcr.2006.03.005 CrossRefGoogle Scholar
  26. 26.
    Heerding DA, Chan G, DeWolf WE et al (2001) 1, 4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI). Bioorg Med Chem Lett 11:2061–2065.  https://doi.org/10.1016/S0960-894X(01)00404-8 CrossRefPubMedGoogle Scholar
  27. 27.
    Kljun J, Scott AJ, Lanišnik Rižner T et al (2014) Synthesis and biological evaluation of organoruthenium complexes with azole antifungal agents. First crystal structure of a tioconazole metal complex. Organometallics 33:1594–1601.  https://doi.org/10.1021/om401096y CrossRefGoogle Scholar
  28. 28.
    Kabbani AT, Hammud HH, Ghannoum AM (2007) Preparation and antibacterial activity of copper and cobalt complexes of 4-chloro-3-nitrobenzoate with a nitrogen donor ligand. Chem Pharm Bull (Tokyo) 55:446–450.  https://doi.org/10.1248/cpb.55.446 CrossRefGoogle Scholar
  29. 29.
    Thimmaiah KN, Chandrappa GT, Sekhar VC (1986) Extraction spectrophotometric investigation of mixed ligand complex of molybdenum(V) with thiocyanate and 4-acetyl-2-(acetylamino)-5-dimethyl-δ2-1,3,4-thiadiazole. Mikrochim Acta 90:277–285.  https://doi.org/10.1007/BF01199270 CrossRefGoogle Scholar
  30. 30.
    Viswanathamurthi P, Karvembu R, Tharaneeswaran V, Natarajan K (2005) Ruthenium(II) complexes containing bidentate Schiff bases and triphenylphosphine or triphenylarsine. J Chem Sci 117:235–238.  https://doi.org/10.1007/BF02709292 CrossRefGoogle Scholar
  31. 31.
    Nfor EN, Asobo PF, Nenwa J et al (2013) Nickel (II) and iron (II) complexes with azole derivatives: synthesis, crystal structures and antifungal activities. Int J Inorg Chem 2013:1–7.  https://doi.org/10.1155/2013/987574 CrossRefGoogle Scholar
  32. 32.
    Urbina JA, Concepcion JL, Montalvetti A et al (2003) Mechanism of action of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the causative agent of Chagas’ disease. Antimicrob Agents Chemother 47:2047–2050.  https://doi.org/10.1128/aac.47.6.2047 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    García-Huertas P, Mejía-Jaramillo AM, Machado CR et al (2017) Prostaglandin F2α synthase in Trypanosoma cruzi plays critical roles in oxidative stress and susceptibility to benznidazole. R Soc Open Sci 4:170773.  https://doi.org/10.1098/rsos.170773 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Aguiar PHN, Furtado C, Repolês BM et al (2013) Oxidative stress and DNA Lesions: the Role of 8-oxoguanine lesions in Trypanosoma cruzi cell viability. PLoS Negl Trop Dis.  https://doi.org/10.1371/journal.pntd.0002279 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Departamento de QuímicaUniversidad de los AndesBogotáColombia
  2. 2.Grupo Biología y Control de Enfermedades InfecciosasUniversidad de AntioquiaMedellínColombia

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