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.

Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents / T.S. Macedo, L. Colina Vegas, M. Da Paixão, M. Navarro, B.C. Barreto, P.C.M. Oliveira, S.G. Macambira, M. Machado, M. Prudêncio, S. D'Alessandro, N. Basilico, D.R.M. Moreira, A.A. Batista, M.B.P. Soares. - In: PARASITOLOGY. - ISSN 0031-1820. - 143:12(2016 Jun), pp. 1543-1556. [10.1017/S0031182016001153]

Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents

S. D'Alessandro;N. Basilico;
2016-06

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.
chloroquine; malaria; organoruthenium complexes; oxidative stress; plasmodium berghei; plasmodium falciparum; parasitology; animal science and zoology; infectious diseases
Settore MED/04 - Patologia Generale
Settore MED/07 - Microbiologia e Microbiologia Clinica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Macedo (2016) Parasitology.pdf

non disponibili

Descrizione: Articolo principale
Tipologia: Publisher's version/PDF
Dimensione 528.01 kB
Formato Adobe PDF
528.01 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/458270
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact