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In Vitro Activity of Ferroquine Against Artemisinin-Based Combination Therapy (ACT)-resistant Plasmodium Falciparum Isolates From Cambodia

In Vitro Activity of Ferroquine Against Artemisinin-Based Combination Therapy (ACT)-resistant Plasmodium Falciparum Isolates From Cambodia

Mélissa Mairet-Khedim, Flore Nardella, Nimol Khim, Saorin Kim, Nimol Kloeung, Sopheakvatey Ke, Chhayleang Kauy, Rotha Eam, Chanra Khean, Alain Pellet, Didier Leboulleux, Rithea Leang, Pascal Ringwald, Jean Christophe Barale, etc.

J Antimicrob Chemother. 2019 Nov 1;74(11):3240-3244.

PMID: 31518407

Abstract:

Background:
Cambodia is the epicentre of resistance emergence for virtually all antimalarial drugs. Selection and spread of parasites resistant to artemisinin-based combination therapy (ACT) is a major threat for malaria elimination, hence the need to renew the pool of effective treatments.
Objectives:
To determine whether ACT resistance haplotypes could have an effect on ferroquine in vitro antimalarial activity.
Methods:
In vitro susceptibility to ferroquine was measured for 80 isolates from Cambodia characterized for their molecular resistance profile to artemisinin, piperaquine and mefloquine.
Results:
Among the 80 isolates tested, the overall median (IQR) IC50 of ferroquine was 10.9 nM (8.7-18.3). The ferroquine median (IQR) IC50 was 8.9 nM (8.1-11.8) for Pfk13 WT parasites and was 12.9 nM (9.5-20.0) for Pfk13 C580Y parasites with no amplification of Pfpm2 and Pfmdr1 genes. The median (IQR) IC50 of ferroquine for Pfk13 C580Y parasites with amplification of the Pfpm2 gene was 17.2 nM (14.5-20.5) versus 9.1 nM (7.9-10.7) for Pfk13 C580Y parasites with amplification of the Pfmdr1 gene.
Conclusions:
Ferroquine exerts promising efficacy against ACT-resistant isolates. Whereas Pfpm2 amplification was associated with the highest parasite tolerance to ferroquine, the susceptibility range observed was in accordance with those measured in ACT resistance-free areas. This enables consideration of ferroquine as a relevant therapeutic option against ACT-resistant malaria.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP185055678	Ferroquine		185055-67-8	Price

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