Targeting the mitochondrial electron transport chain of Plasmodium falciparum: new strategies towards the development of improved antimalarials for the elimination era.

Nixon, Gemma, Pidathala, Chandrakala, Shone, Alison E, Antoine, Thomas, Fisher, Nicholas, O'Neill, Paul M, Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192 and Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595 (2013) 'Targeting the mitochondrial electron transport chain of Plasmodium falciparum: new strategies towards the development of improved antimalarials for the elimination era.'. Future medicinal chemistry, Vol 5, Issue 13, pp. 1573-1591.

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Abstract

Despite intense efforts, there has not been a truly new antimalarial, possessing a novel mechanism of action, registered for over 10 years. By virtue of a novel mode of action, it is hoped that the global challenge of multidrug-resistant parasites can be overcome, as well as developing drugs that possess prophylaxis and/or transmission-blocking properties, towards an elimination agenda. Many target-based and whole-cell screening drug development programs have been undertaken in recent years and here an overview of specific projects that have focused on targeting the parasite's mitochondrial electron transport chain is presented. Medicinal chemistry activity has largely focused on inhibitors of the parasite cytochrome bc1 Complex (Complex III) including acridinediones, pyridones and quinolone aryl esters, as well as inhibitors of dihydroorotate dehydrogenase that includes triazolopyrimidines and benzimidazoles. Common barriers to progress and opportunities for novel chemistry and potential additional electron transport chain targets are discussed in the context of the target candidate profiles for uncomplicated malaria.

Item Type:	Article
Uncontrolled Keywords:	Plasmodium falciparum; Anti-malarials; Drug development
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.4155/fmc.13.121
Depositing User:	Mary Creegan
Date Deposited:	07 Nov 2014 15:37
Last Modified:	25 Jan 2022 10:06
URI:	https://archive.lstmed.ac.uk/id/eprint/4531

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