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

• Published in: Malaria Journal
• Main Authors: 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2012
• Subjects: Malaria; Plasmodium falciparum; Anti-malarial; In vitro; Resistance; Pyronaridine; Piperaquine; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic; Rho
• Online Access: https://doi.org/10.1186/1475-2875-11-45; https://doaj.org/article/9ec13234059144b18c4e63182e29403b

Abstract 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.