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Novel inhibitors of the Plasmodium falciparum electron transport chain

Published online by Cambridge University Press:  08 January 2014

P. A. STOCKS ,
V. BARTON ,
T. ANTOINE ,
G. A. BIAGINI ,
S. A. WARD  and
P. M. O'NEILL
P. A. STOCKS
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
V. BARTON
Affiliation:
Department of Chemistry, University of Liverpool, P.O. Box 147, Liverpool, L69 3BX, UK
T. ANTOINE
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
G. A. BIAGINI
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
S. A. WARD
Affiliation:
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
P. M. O'NEILL*
Affiliation:
Department of Chemistry, University of Liverpool, P.O. Box 147, Liverpool, L69 3BX, UK
*
*Corresponding author: Department of Chemistry, University of Liverpool, P.O. Box 147, Liverpool, L69 3BX, UK. Tel: 0151 794 3553. E-mail: p.m.oneill01@liv.ac.uk
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Summary

Due to an increased need for new antimalarial chemotherapies that show potency against Plasmodium falciparum, researchers are targeting new processes within the parasite in an effort to circumvent or delay the onset of drug resistance. One such promising area for antimalarial drug development has been the parasite mitochondrial electron transport chain (ETC). Efforts have been focused on targeting key processes along the parasite ETC specifically the dihydroorotate dehydrogenase (DHOD) enzyme, the cytochrome bc1 enzyme and the NADH type II oxidoreductase (PfNDH2) pathway. This review summarizes the most recent efforts in antimalarial drug development reported in the literature and describes the evolution of these compounds.

Keywords

Antimalarialdrug developmentmitochondrialdihydroorotate dehydrogenasecytochrome bc1PfNADH IIstructure-activity relationships
Type
Research Article
Information
Parasitology , Volume 141 , Issue 1: Symposia of the British Society for Parasitology volume 49 Emerging paradigms in anti-infective drug design , January 2014 , pp. 50 - 65
Copyright
Copyright © Cambridge University Press 2014 

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