Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.
Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[RuII(η2-O2CR)(dppm)2]PF6, with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes.
['Costa|Mônica S|MS|', 'Gonçalves|Yasmim G|YG|', 'Nunes|Débora C O|DCO|', 'Napolitano|Danielle R|DR|', 'Maia|Pedro I S|PIS|', 'Rodrigues|Renata S|RS|', 'Rodrigues|Veridiana M|VM|', 'Von Poelhsitz|Gustavo|G|', 'Yoneyama|Kelly A G|KAG|']
D000818:Animals D000981:Antiprotozoal Agents D056831:Coordination Complexes D006790:Host-Parasite Interactions D007891:Leishmania D007896:Leishmaniasis D008264:Macrophages D051379:Mice D000067996:RAW 264.7 Cells D012428:Ruthenium
Ruthenium(II) complexes Leishmania Cytotoxicity Infectivity inhibition