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

Author(s):Show less -

Espuri, Patricia Ferreira ^{[1, 2]} ; dos Reis, Larissa Luiza ^[1] ; Peloso, Eduardo de Figueiredo ^[3] ; Gontijo, Vanessa Silva ^[4] ; Colombo, Fabio Antonio ^[1] ; Nunes, Juliana Barbosa ^[1] ; de Oliveira, Carine Ervolino ^[1] ; de Almeida, Eduardo T. ^[4] ; Silva, Debora E. S. ^[5] ; Bortoletto, Jessica ^[5] ; Segura, Daniel Fonseca ^[5] ; Netto, Adelino V. G. ^[5] ; Marques, Marcos Jose ^{[1, 2]}

Affiliation

^[1] Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, Lab Parasitol, BR-37130001 Alfenas, MG - Brazil

^[2] Univ Fed Alfenas, Inst Biomed Sci, 700 Gabriel Monteiro da Silva St, BR-37130000 Alfenas, MG - Brazil

^[3] Univ Fed Alfenas, Inst Biomed Sci, Dept Biochem, BR-37130000 Alfenas, MG - Brazil

^[4] Univ Fed Alfenas, Inst Chem, Lab Res Med Chem, BR-37133840 Alfenas, MG - Brazil

^[5] Univ Estadual Paulista, UNESP, Inst Chem, POB 355, BR-14801970 Araraquara, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY; v. 24, n. 3, p. 419-432, MAY 2019.
• Web of Science Citations: 2

Abstract

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), {[}Ag-2(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 1.88M, respectively) and Lc (IC50=9.35 and 8.05M, 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. {[}GRAPHICS] (AU)

• FAPESP's process: 16/17711-5 - INVESTIGATION OF THE ANTITUMOR POTENTIAL OF PALLADIUM(II) COMPOUNDS CONTAINING ORTHOMETALLATED OR N,S-DONOR LIGANDS
• Grantee: Adelino Vieira de Godoy Netto
• Support Opportunities: Regular Research Grants