In vitro evaluation of antileishmanial activity of copper (I) complexes

Abstract

In the research for the development of new drugs for the therapy of American tegumentary leishmaniasis, copper has been studied for its antileishmania activity. This study aims to report the activity of three copper(I) complexes on parasites of the species L. amazonensis and L. guyanensis. The metal complexes were tested according to in vitro antileishmanial assays, against promastigote and amastigote forms of the most prevalent species in the state of Amazonas, Brazil. Cytotoxicity of the complexes was evaluated in murine macrophage-like cell line (MJ774). The results of the in vitro assays indicated that, among the copper complexes tested, the homoleptic phosphine complex [Cu(thp)4][PF6](thp=tris-hydroxymethylphosphine) presented promising activity against the evolutionary forms of L. amazonensis, and obtained a IC50 of 26.45 and 24.61 µM in a period of 48 and 72 h, respectively. The results for copper complex at concentration 160 µM in amastigote forms showed a decrease in the infection index (32% of infected cells) and, in the cytotoxicity assay with MJ774, 52.43% of cell viability was observed. The results showed that the complex [Cu(thp)4][PF6] presented significant biological activity, indicating a need for future in vivo studies.

Antileishmanial and Anti‐Chikungunya Activity of Cu(I)‐N‐Heterocyclic Carbenes

“…The leishmanicidal activity followed the same trend in the series, revealing the same structure/activity relationship previously discussed [61,66,67] . Although compound ( 6 ) has the highest SI value (8.84), IC 50 <1 μM, and a low infection rate and infectivity index value at all concentrations, we emphasize that the literature considers a good leishmanicidal candidate one that has an IC 50 less than or equal to 10 μM against intracellular amastigotes and selectivity greater than or equal to 10 against the parasite towards the host cell.…”

“…The high lipophilicity and charge of compound ( 4 ) may be considered critical properties that caused the higher cytotoxicity to the host cell. Comparing this work with the results of Touj and colleagues, novel designs should consider a balance between NHC steric hindrance and lipophilicity [14,61,62,68] …”

“…While compound ( 5 ) presents speciation when in solution with polar solvents (DMSO) and the highest antioxidant activity value and a lower lipophilicity value than ( 4 ), demonstrating that probably the existence of an equilibrium in solution has increased its activity when compared to compound ( 4 ), and its toxicity when compared to ( 6 ). Though this compound presents a lipophilicity value and antioxidant activity close to ( 5 ), it is less toxic to macrophages and more selective to the parasite [61–64] …”