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Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

BACKGROUND: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaq...

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Autores principales: Pascual, Aurélie, Parola, Philippe, Benoit-Vical, Françoise, Simon, Fabrice, Malvy, Denis, Picot, Stéphane, Delaunay, Pascal, Basset, Didier, Maubon, Danièle, Faugère, Bernard, Ménard, Guillaume, Bourgeois, Nathalie, Oeuvray, Claude, Didillon, Eric, Rogier, Christophe, Pradines, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305508/
https://www.ncbi.nlm.nih.gov/pubmed/22333675
http://dx.doi.org/10.1186/1475-2875-11-45
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author Pascual, Aurélie
Parola, Philippe
Benoit-Vical, Françoise
Simon, Fabrice
Malvy, Denis
Picot, Stéphane
Delaunay, Pascal
Basset, Didier
Maubon, Danièle
Faugère, Bernard
Ménard, Guillaume
Bourgeois, Nathalie
Oeuvray, Claude
Didillon, Eric
Rogier, Christophe
Pradines, Bruno
author_facet Pascual, Aurélie
Parola, Philippe
Benoit-Vical, Françoise
Simon, Fabrice
Malvy, Denis
Picot, Stéphane
Delaunay, Pascal
Basset, Didier
Maubon, Danièle
Faugère, Bernard
Ménard, Guillaume
Bourgeois, Nathalie
Oeuvray, Claude
Didillon, Eric
Rogier, Christophe
Pradines, Bruno
author_sort Pascual, Aurélie
collection PubMed
description BACKGROUND: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). METHODS: The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours (3)H-hypoxanthine uptake inhibition method. RESULTS: The IC(50 )values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC(50 )and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. CONCLUSIONS: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs.
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spelling pubmed-33055082012-03-16 Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum Pascual, Aurélie Parola, Philippe Benoit-Vical, Françoise Simon, Fabrice Malvy, Denis Picot, Stéphane Delaunay, Pascal Basset, Didier Maubon, Danièle Faugère, Bernard Ménard, Guillaume Bourgeois, Nathalie Oeuvray, Claude Didillon, Eric Rogier, Christophe Pradines, Bruno Malar J Research BACKGROUND: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). METHODS: The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours (3)H-hypoxanthine uptake inhibition method. RESULTS: The IC(50 )values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC(50 )and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. CONCLUSIONS: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs. BioMed Central 2012-02-14 /pmc/articles/PMC3305508/ /pubmed/22333675 http://dx.doi.org/10.1186/1475-2875-11-45 Text en Copyright ©2012 Pascual et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Pascual, Aurélie
Parola, Philippe
Benoit-Vical, Françoise
Simon, Fabrice
Malvy, Denis
Picot, Stéphane
Delaunay, Pascal
Basset, Didier
Maubon, Danièle
Faugère, Bernard
Ménard, Guillaume
Bourgeois, Nathalie
Oeuvray, Claude
Didillon, Eric
Rogier, Christophe
Pradines, Bruno
Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title_full Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title_fullStr Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title_full_unstemmed Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title_short Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
title_sort ex vivo activity of the act new components pyronaridine and piperaquine in comparison with conventional act drugs against isolates of plasmodium falciparum
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305508/
https://www.ncbi.nlm.nih.gov/pubmed/22333675
http://dx.doi.org/10.1186/1475-2875-11-45
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