title: Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents.
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.
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Taís S
authors.initials: TS
authors.lastname: Macedo
authors.affiliation: Departamento de Química,UFSCAR,13565-905,São Carlos,SP,Brazil.
authors.forename: Legna
authors.initials: L
authors.lastname: Colina-Vegas
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: DA Paixão
authors.affiliation: INMETRO,Xerém,25250-020,Rio de Janeiro,RJ,Brazil.
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Breno C
authors.initials: BC
authors.lastname: Barreto
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Poliana C M
authors.initials: PC
authors.lastname: Oliveira
authors.affiliation: Instituto de Ciências da Saúde,Universidade Federal da Bahia,CEP 40110-100,Salvador,BA,Brazil.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Macambira
authors.affiliation: Instituto de Medicina Molecular,Faculdade de Medicina,Universidade de Lisboa,1649-028 Lisboa,Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Machado
authors.affiliation: Instituto de Medicina Molecular,Faculdade de Medicina,Universidade de Lisboa,1649-028 Lisboa,Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari,Università degli Studi di Milano,20133 Milan,Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: D'Alessandro
authors.affiliation: Dipartimento di Scienze Biomediche,Chirurgiche e Odontoiatriche,Universitá degli Studi di Milano,20133 Milan,Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Diogo R M
authors.initials: DR
authors.lastname: Moreira
authors.affiliation: Departamento de Química,UFSCAR,13565-905,São Carlos,SP,Brazil.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
authors.affiliation: FIOCRUZ,Centro de Pesquisas Gonçalo Moniz,40296-710,Salvador,BA,Brazil.
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D012428:Ruthenium / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D009942:Organometallic Compounds; D012428:Ruthenium; D002738:Chloroquine
keywords: Malaria; Plasmodium berghei; Plasmodium falciparum; chloroquine; organoruthenium complexes; oxidative stress