Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9649
Title: Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies
Authors: Souza, Nicolli Bellotti de
Andrade, Isabel Mayer de
Carneiro, Paula Fernandes
Jardim, Guilherme AM
Melo, Isadora MM de
Silva Júnior, Eufrânio N da
Krettli, Antoniana Ursine
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brasil
Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Laboratório de Química Sintética e Heterocíclica. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Laboratório de Química Sintética e Heterocíclica. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Departamento de Química. Laboratório de Química Sintética e Heterocíclica. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malária. Belo Horizonte, MG, Brasil
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.
Keywords: Plasmodium falciparum
Plasmodium berghei
antimalarials
lapachol
quinones
phenazines
Issue Date: 2014
Publisher: Fundação Oswaldo Cruz
Citation: SOUZA, Nicolli Bellotti de et al. Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies. Mem Inst Oswaldo Cruz, v. 109, n. 5, p. 254-552, 2014
DOI: 10.1590/0074-0276130603
ISSN: 1678-8060
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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