Dataset Information

Biological evaluation of hydroxynaphthoquinones as anti-malarials.

ABSTRACT:

Background

The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.

Methods

Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS.

Results

Four compounds demonstrated IC50s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50??mit of 16 ?M. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 ?M.

Conclusions

N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials.

SUBMITTER: Schuck DC

PROVIDER: S-EPMC3726445 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Biological evaluation of hydroxynaphthoquinones as anti-malarials.

Schuck Desiree C DC Ferreira Sabrina B SB Cruz Laura N LN da Rocha David R DR Moraes Miriam S MS Nakabashi Myna M Rosenthal Philip J PJ Ferreira Vitor F VF Garcia Celia R S CR

Malaria journal 20130710

<h4>Background</h4>The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.<h4>Methods</h4>Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells ...[more]

PMID: 23841934

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Dataset Information

Biological evaluation of hydroxynaphthoquinones as anti-malarials.

Background

Methods

Results

Conclusions

Publications

Biological evaluation of hydroxynaphthoquinones as anti-malarials.

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