ArticleMalaria journal2019
Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel ring-stage survival assay.
Article in Malaria journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
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- Artefenomel Regioisomer RLA-3107 Is a Promising Lead for the Discovery of Next-Generation Endoperoxide Antimalarials.ACS medicinal chemistry letters · 2023Article
- Naturally Acquired Kelch13 Mutations in Plasmodium falciparum Strains ModulateMicrobiology spectrum · 2022Article
- Cytochrome P450-Mediated Metabolism and CYP Inhibition for the Synthetic Peroxide Antimalarial OZ439.ACS infectious diseases · 2021Article
- A Proteasome Mutation SensitizesACS infectious diseases · 2021Article
- Enantiospecific antitrypanosomal in vitro activity of eflornithine.PLoS neglected tropical diseases · 2021Article
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- Antimalarial Trioxolanes with Superior Drug-Like Properties and In Vivo Efficacy.ACS infectious diseases · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug efficacy against kelch 13 mutant malaria parasites can be determined in vitro with the ring-stage survival assay (RSA). The conventional assay protocol reflects the exposure profile of dihydroartemisinin.
methodsTaking into account that other anti-malarial peroxides, such as the synthetic ozonides OZ439 (artefenomel) and OZ609, have different pharmacokinetics, the RSA was adjusted to the concentration-time profile of these ozonides in humans and a novel, semi-automated readout was introduced.
resultsWhen tested at clinically relevant parameters, it was shown that OZ439 and OZ609 are active against the Plasmodium falciparum clinical isolate Cam3.I
conclusionIf the in vitro RSA does indeed predict the potency of compounds against parasites with increased tolerance to artemisinin and its derivatives, then the herein presented data suggest that following drug-pulses of at least 48 h, OZ439 and OZ609 will be highly potent against kelch 13 mutant isolates, such as P. falciparum Cam3.I
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