Blood shizonticidal activities of phenazines and naphthoquinoidal
compounds against Plasmodium falciparum in vitro and in mice malaria
studies |
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Authors: | Nicolli Bellotti de Souza Isabel M de Andrade Paula F Carneiro Guilherme AM Jardim Isadora MM de Melo Eufranio N da Silva Júnior Antoniana Ursine Krettli |
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Institution: | 1.Laboratório de Malária, Centro de Pesquisas René-Rachou-Fiocruz, Belo Horizonte, MG, Brasil;2.Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil;3.Laboratório de Química Sintética e Heterocíclica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil |
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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. |
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Keywords: | antimalarials quinones phenazines lapachol Plasmodium falciparum Plasmodium berghei |
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