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  • Title: Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents.
    Author: Macedo TS, Colina-Vegas L, DA Paixão M, Navarro M, Barreto BC, Oliveira PC, Macambira SG, Machado M, Prudêncio M, D'Alessandro S, Basilico N, Moreira DR, Batista AA, Soares MB.
    Journal: Parasitology; 2016 Oct; 143(12):1543-56. PubMed ID: 27439976.
    Abstract:
    We report the pharmacological activity of organoruthenium complexes containing chloroquine (CQ) as a chelating ligand. The complexes displayed intraerythrocytic activity against CQ-sensitive 3D7 and CQ-resistant W2 strains of Plasmodium falciparum, with potency and selectivity indexes similar to those of CQ. Complexes displayed activity against all intraerythrocytic stages, but moderate activity against Plasmodium berghei liver stages. However, unlike CQ, organoruthenium complexes impaired gametocyte viability and exhibited fast parasiticidal activity against trophozoites for P. falciparum. This functional property results from the ability of complexes to quickly induce oxidative stress. The parasitaemia of P. berghei-infected mice was reduced by treatment with the complex. Our findings demonstrated that using chloroquine for the synthesis of organoruthenium complexes retains potency and selectivity while leading to an increase in the spectrum of action and parasite killing rate relative to CQ.
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