Synthesis and evaluation of the antileishmanial activity of silver compounds containing imidazolidine-2-thione

  • Patrícia Ferreira EspuriEmail author
  • Larissa Luiza dos Reis
  • Eduardo de Figueiredo Peloso
  • Vanessa Silva Gontijo
  • Fábio Antônio Colombo
  • Juliana Barbosa Nunes
  • Carine Ervolino de Oliveira
  • Eduardo T. De Almeida
  • Débora E. S. Silva
  • Jessica Bortoletto
  • Daniel Fonseca Segura
  • Adelino V. G. Netto
  • Marcos José MarquesEmail author


A new series of silver compounds could be of interest on designing new drugs for the treatment of leishmaniasis. The compounds [Ag(phen)(imzt)]NO3(1), [Ag(phen)(imzt)]CF3SO3(2), [Ag(phen)2](BF4)·H2O (3), [Ag2(imzt)6](NO3)2(4), and imzt have been synthesized and evaluated in vitro for antileishmanial activity against Leishmania. (L.) amazonensis (La) and L. (L.) chagasi (Lc), and two of them were selected for in vivo studies. In addition to investigating the action on Leishmania, their effects on the hydrogen peroxide production and cysteine protease inhibition have also been investigated. As for antileishmanial activity, compound (4) was the most potent against promastigote and amastigote forms of La (IC50 = 4.67 and 1.88 μM, respectively) and Lc (IC50 = 9.35 and 8.05 μM, respectively); and comparable to that of amphotericin B, reference drug. Beside showing excellent activity, it also showed a low toxicity. In the in vivo context, compound (4) reduced the number of amastigotes in the liver and spleen when compared to the untreated group. In evaluating the effect of the compounds on Leishmania, the level of hydrogen peroxide production was maintained between the lag and log phases; however, in the treatment with compound (4) it was possible to observe a reduction of 25.44 and 49.13%, respectively, in the hydrogen peroxide rates when compared to the lag and log phases. It was noticed that the presence of a nitrate ion and imzt in compound (4) was important for the modulation of the antileishmanial activity. Thus, this compound can represent a potentially new drug for the treatment of leishmaniasis.

Graphical abstract


Leishmania Silver compounds Biological effects 



This work was sponsored by Grants from CNPq (proc. 487092/2012-0, INCT-INOFAR), FAPESP (2016/17711-5), CAPES and FAPEMIG.

Supplementary material

775_2019_1657_MOESM1_ESM.pdf (79 kb)
Supplementary material 1 (PDF 78 kb)


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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Patrícia Ferreira Espuri
    • 1
    • 5
    Email author
  • Larissa Luiza dos Reis
    • 1
  • Eduardo de Figueiredo Peloso
    • 2
  • Vanessa Silva Gontijo
    • 3
  • Fábio Antônio Colombo
    • 1
  • Juliana Barbosa Nunes
    • 1
  • Carine Ervolino de Oliveira
    • 1
  • Eduardo T. De Almeida
    • 3
  • Débora E. S. Silva
    • 4
  • Jessica Bortoletto
    • 4
  • Daniel Fonseca Segura
    • 4
  • Adelino V. G. Netto
    • 4
  • Marcos José Marques
    • 1
    • 5
    Email author
  1. 1.Laboratory of Parasitology, Department of Pathology and Parasitology, Institute of Biomedical SciencesUniversidade Federal de AlfenasAlfenasBrazil
  2. 2.Department of Biochemistry, Institute of Biomedical SciencesUniversidade Federal de AlfenasAlfenasBrazil
  3. 3.Laboratory of Researche on Medicinal Chemistry, Institute of ChemistryUniversidade Federal de AlfenasAlfenasBrazil
  4. 4.Institute of ChemistryUNESP-Univ. Estadual PaulistaAraraquaraBrazil
  5. 5.Institute of Biomedical SciencesFederal University of AlfenasAlfenasBrazil

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