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Updated: Aug 17, 2026
Protocols for Testing the Toxicity of Novel Insecticidal Chemistries to Mosquitoes
Published on: February 13, 2019
Anti-malarial ozonides OZ439 and OZ609 tested at clinically relevant compound exposure parameters in a novel
Annabelle Walz1,2, Didier Leroy3, Nicole Andenmatten3
1Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.
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.IR539T.
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.IR539T.
