Skip to the content

Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate

Matthews, H, Usman-Idris, M, Khan, F, Read, M and Nirmalan, NJ 2013, 'Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate' , Malaria Journal, 12 (1) , p. 359.

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

Background Drug repurposing or repositioning refers to the usage of existing drugs in diseases other than those it was originally used for. For diseases like malaria, where there is an urgent need for active drug candidates, the strategy offers a route to significantly shorten the traditional drug development pipelines. Preliminary high-throughput screens on patent expired drug libraries have recently been carried out for Plasmodium falciparum. This study reports the systematic and objective further interrogation of selected compounds reported in these studies, to enable their repositioning as novel stand-alone anti-malarials or as combinatorial partners. Methods SYBR Green flow cytometry and micro-titre plate assays optimized in the laboratory were used to monitor drug susceptibility of in vitro cultures of P. falciparum K1 parasite strains. Previously described fixed-ratio methods were adopted to investigate drug interactions. Results Emetine dihydrochloride hydrate, an anti-protozoal drug previously used for intestinal and tissue amoebiasis was shown to have potent inhibitory properties (IC50 doses of ~ 47nM) in the multidrug resistant K1 strain of P. falciparum. The sum 50% fractional inhibitory concentration ([n-ary summation]FIC50, 90) of the interaction of emetine dihydrochloride hydrate and dihydroartemisinin against the KI strains of P. falciparum ranged from 0.88-1.48. Conclusion The results warrant further investigation of emetine dihydrochloride hydrate as a potential stand-alone anti-malarial option. The interaction between the drug and the current front line dihydroartemisinin ranged from additive to mildly antagonistic in the fixed drug ratios tested.

Item Type: Article
Uncontrolled Keywords: Drug repositioning; Antimalarial chemotherapy; Emetine; Dihydroartemisinin; Drug susceptibility assays; Flow cytometry
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Schools > School of Environment and Life Sciences
Journal or Publication Title: Malaria Journal
Publisher: BioMed central
Refereed: Yes
ISSN: 1475-2875
Related URLs:
Funders: Non funded research
Depositing User: S Rafiq
Date Deposited: 15 Oct 2013 17:38
Last Modified: 30 Nov 2015 23:55
URI: http://usir.salford.ac.uk/id/eprint/29560

Actions (login required)

Edit record (repository staff only) Edit record (repository staff only)

Downloads

Downloads per month over past year