Dados do Trabalho

Título

Gold complexes with low citoxicity as promising drug candidates against Leishmania amazonensis

Introdução

Leishmaniasis, one of the most neglected diseases in the world, is caused by protozoan parasites of Leishmania genus, that leads to cutaneous (localized, mucosal, diffuse, disseminated) and/or visceral manifestations depending on the causative species. In all clinical forms, chemotherapeutic options are limited due to long schemes of parenteral administration of very toxic drugs, especially antimony-based compounds. Based on these bottlenecks, several metal complexes have been investigated as leishmanicidal agents, such as Gold (Au), Palladium (Pd), Copper (Cu), Silver (Ag) and Ruthenium (Ru) as they may present more than one mechanism of action capable of reaching multiple targets. Regarding Au complexes, leishmanicidal in vitro investigation of several complexes with different ligands dates from the 80s.

Objetivo (s)

In this scenario, we evaluated L. amazonensis growth inhibition in vitro after treatment with four new gold-based complexes.

Material e Métodos

Firstly, L. amazonensis promastigotes were incubated with decreasing concentrations (25, 12,5, 6,25, 3,125, 1,6 μM) compounds A1, A2, A3, and A5 for 24h and the viability was evaluated by the MTT method. For the cytotoxicity assay, bone marrow-derived macrophages were incubated for 24h and CC50 values were established. Next, macrophages were infected with L. amazonensis promastigotes (MOI=5) and incubated with the gold-based complexes at 15, 10, and 5 μM for 24h.

Resultados e Conclusão

The following EC50 were established from dose-response curves: A1=5.0, A2=2.5, A3=2.3, A5=8.1 μM. The CC50 values were A1=115.4, A2=116.3, A3=117.0, A5=118.9 μM. Interestingly, promising selectivity indexes for the four gold complexes were 23, 46.5, 50.8, and 14.6 for A1, A2, A3, and A5, respectively. A significant reduction in intracellular amastigote burden was observed compared to untreated infections for A2 (42.5%) and A3 (34.7%) at 15 μM. In conclusion, in vitro assays demonstrated that our gold complexes may be an effective alternative for leishmaniasis treatment and deserves further in vivo investigation.

Palavras-chave

Gold complexes, leishmaniasis, treatment

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