ArticleAntimicrobial agents and chemotherapy2014
Ex vivo activity of endoperoxide antimalarials, including artemisone and arterolane, against multidrug-resistant Plasmodium falciparum isolates from Cambodia.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Antigenic strain diversity predicts different biogeographic patterns of maintenance and decline of anti-malarial drug resistance.bioRxiv : the preprint server for biology · 2023Article
- Efficacies and ADME properties of redox active methylene blue and phenoxazine analogues for use in new antimalarial triple drug combinations with amino-artemisinins.Frontiers in pharmacology · 2023Article
- The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood StagePharmaceutics · 2021Article
- Toward New Transmission-Blocking Combination Therapies: Pharmacokinetics of 10-Amino-Artemisinins and 11-Aza-Artemisinin and Comparison with Dihydroartemisinin and Artemether.Antimicrobial agents and chemotherapy · 2021Article
- Niclosamide Is Active In Vitro against Mycetoma Pathogens.Molecules (Basel, Switzerland) · 2021Article
- Efficient Treatment of Experimental Cerebral Malaria by an Artemisone-SMEDDS System: Impact of Application Route and Dosing Frequency.Antimicrobial agents and chemotherapy · 2021Article
- Optimal 10-Aminoartemisinins With Potent Transmission-Blocking Capabilities for New Artemisinin Combination Therapies-Activities Against Blood StageFrontiers in chemistry · 2019Article
- Artemisone and Artemiside Are Potent Panreactive Antimalarial Agents That Also Synergize Redox Imbalance in Plasmodium falciparum Transmissible Gametocyte Stages.Antimicrobial agents and chemotherapy · 2018Article
- Alternatives to currently used antimalarial drugs: in search of a magic bullet.Infectious diseases of poverty · 2016Review
- Endoperoxide Drug Cross-Resistance Patterns for Plasmodium falciparum Exhibiting an Artemisinin Delayed-Clearance Phenotype.Antimicrobial agents and chemotherapy · 2016Article
- Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions.Journal of clinical microbiology · 2015Article
- Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance.Antimicrobial agents and chemotherapy · 2015Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel synthetic endoperoxides are being evaluated as new components of artemisinin combination therapies (ACTs) to treat artemisinin-resistant Plasmodium falciparum malaria. We conducted blinded ex vivo activity testing of fully synthetic (OZ78 and OZ277) and semisynthetic (artemisone, artemiside, artesunate, and dihydroartemisinin) endoperoxides in the histidine-rich protein 2 enzyme-linked immunosorbent assay against 200 P. falciparum isolates from areas of artemisinin-resistant malaria in western and northern Cambodia in 2009 and 2010. The order of potency and geometric mean (GM) 50% inhibitory concentrations (IC50s) were as follows: artemisone (2.40 nM) > artesunate (8.49 nM) > dihydroartemisinin (11.26 nM) > artemiside (15.28 nM) > OZ277 (31.25 nM) > OZ78 (755.27 nM). Ex vivo activities of test endoperoxides positively correlated with dihydroartemisinin and artesunate. The isolates were over 2-fold less susceptible to dihydroartemisinin than the artemisinin-sensitive P. falciparum W2 clone and showed sensitivity comparable to those with test endoperoxides and artesunate, with isolate/W2 IC50 susceptibility ratios of <2.0. All isolates had P. falciparum chloroquine resistance transporter mutations, with negative correlations in sensitivity to endoperoxides and chloroquine. The activities of endoperoxides (artesunate, dihydroartemisinin, OZ277, and artemisone) significantly correlated with that of the ACT partner drug, mefloquine. Isolates had mutations associated with clinical resistance to mefloquine, with 35% prevalence of P. falciparum multidrug resistance gene 1 (pfmdr1) amplification and 84.5% occurrence of the pfmdr1 Y184F mutation. GM IC50s for mefloquine, lumefantrine, and endoperoxides (artesunate, dihydroartemisinin, OZ277, OZ78, and artemisone) correlated with pfmdr1 copy number. Given that current ACTs are failing potentially from reduced sensitivity to artemisinins and partner drugs, newly identified mutations associated with artemisinin resistance reported in the literature and pfmdr1 mutations should be examined for their combined contributions to emerging ACT resistance.
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