title: In vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate.
abstract: Recently published data suggest that artemisinin derivatives and synthetic peroxides, such as the ozonides OZ277 and OZ439, have a similar mode of action. Here the cross-resistance of OZ277 and OZ439 and four additional next-generation ozonides was probed against the artemisinin-resistant clinical isolate Plasmodium falciparum Cam3.I, which carries the K13-propeller mutation R539T (Cam3.IR539T).
  
  
  
  The previously described in vitro ring-stage survival assay (RSA0-3h) was employed and a simplified variation of the original protocol was developed.
  
  
  
  At the pharmacologically relevant concentration of 700 nM, all six ozonides were highly effective against the dihydroartemisinin-resistant P. falciparum Cam3.IR539Tparasites, showing a per cent survival ranging from <0.01 to 1.83%. A simplified version of the original RSA0-3hmethod was developed and gave similar results, thus providing a practical drug discovery tool for further optimization of next-generation anti-malarial peroxides.
  
  
  
  The absence of in vitro cross-resistance against the artemisinin-resistant clinical isolate Cam3.IR539Tsuggests that ozonides could be effective against artemisinin-resistant P. falciparum. How this will translate to the human situation in clinical settings remains to be investigated.
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.|University of Basel, Petersplatz 1, 4001, Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Baumgärtner
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.|University of Basel, Petersplatz 1, 4001, Basel, Switzerland.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Jourdan
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.|University of Basel, Petersplatz 1, 4001, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.affiliation: Medicines for Malaria Venture, ICC, 20 Route de Pré-Bois, PO Box 1826, 1215, Geneva, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Blasco
authors.affiliation: Medicines for Malaria Venture, ICC, 20 Route de Pré-Bois, PO Box 1826, 1215, Geneva, Switzerland.
authors.forename: Brice
authors.initials: B
authors.lastname: Campo
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.|University of Basel, Petersplatz 1, 4001, Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mäser
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland. sergio.wittlin@unibas.ch.|University of Basel, Petersplatz 1, 4001, Basel, Switzerland. sergio.wittlin@unibas.ch.
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D004351:Drug Resistance; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D013141:Spiro Compounds; C489136:arterolane; C031327:artemisinin; D000218:Adamantane; C558165:artefenomel
keywords: Artemisinin; Cam3.IR539T; Drug resistance; Ozonide; Plasmodium falciparum; Ring-stage survival assay