title: Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies.
abstract: Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René-Rachou-Fiocruz, Belo Horizonte, MG, Brasil.
authors.forename: Nicolli Bellotti
authors.initials: NB
authors.lastname: de Souza
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René-Rachou-Fiocruz, Belo Horizonte, MG, Brasil.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: de Andrade
authors.affiliation: Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Paula F
authors.initials: PF
authors.lastname: Carneiro
authors.affiliation: Laboratório de Química Sintética e Heterocíclica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Guilherme A M
authors.initials: GA
authors.lastname: Jardim
authors.affiliation: Laboratório de Química Sintética e Heterocíclica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Isadora M M
authors.initials: IM
authors.lastname: de Melo
authors.affiliation: Laboratório de Química Sintética e Heterocíclica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva Júnior
authors.affiliation: Laboratório de Malária, Centro de Pesquisas René-Rachou-Fiocruz, Belo Horizonte, MG, Brasil.
authors.forename: Antoniana Ursine
authors.initials: AU
authors.lastname: Krettli
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010619:Phenazines / Q000737:chemistry / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D009285:Naphthoquinones; D010619:Phenazines
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