Mem Inst Oswaldo Cruz, Rio de Janeiro, 113(6) june 2018
Original Article

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Nicolli Bellotti de Souza1, Isabel M de Andrade1, Paula F Carneiro2, Guilherme AM Jardim3, Isadora MM de Melo3, Eufrânio N da Silva Júnior3,+, Antoniana Ursine Krettli1,+

1Laboratório de Malária, Centro de Pesquisas René-Rachou-Fiocruz, Belo Horizonte, MG, Brasil
2Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
3Laboratório de Química Sintética e Heterocíclica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

Page: 546-552 DOI: 10.1590/0074-0276130603
659 views 146 downloads
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 lethalu00a0dose 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.

Financial support: CAPES, CNPq/FAPEMIG, MCT/CNPq/CT-Saúde/MS/SCTIE/DECIT (480719/2012-8, 480719/2012-8), Project Universal MCTI/CNPq (14/2012) (480719/2012-8), UFMG (to ENSJ)
+ Corresponding authors: akrettli@cpqrr.fiocruz.br , eufranio@ufmg.br
Received 30 December 2013
Accepted 5 May 2014

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program

logo fiocruz logo governo
logo faperj logo cnpq marca capes