Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel ring-stage survival assay
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4522972
Author(s) Walz, A.; Leroy, D.; Andenmatten, N.; Mäser, P.; Wittlin, S.
Author(s) at UniBasel Walz, Annabelle
Mäser, Pascal
Wittlin, Sergio
Year 2019
Title Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel ring-stage survival assay
Journal Malaria journal
Volume 18
Number 1
Pages / Article-Number 427
Abstract BACKGROUND: Drug 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. METHODS: Taking 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. RESULTS: When tested at clinically relevant parameters, it was shown that OZ439 and OZ609 are active against the Plasmodium falciparum clinical isolate Cam3.I(R539T). CONCLUSION: If 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(R539T).
Publisher BioMed Central
ISSN/ISBN 1475-2875
edoc-URL https://edoc.unibas.ch/73600/
Full Text on edoc Available
Digital Object Identifier DOI 10.1186/s12936-019-3056-8
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/31849323
ISI-Number WOS:000506910700002
Document type (ISI) Journal Article
 
   

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