In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts

Joachim Müller, Vreni Balmer, Pablo Winzer, Mahbubur Rahman, Vera Manser, Richard K. Haynes, Andrew Hemphill

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

From a panel of 34 artemisinin derivatives tested in vitro, artemisone, GC007 and GC012 were most efficacious at inhibiting Neospora caninum replication (IC50 values of 3-54 nM), did not notably impair the invasiveness of tachyzoites and were non-toxic for human foreskin fibroblasts (HFFs). Transmission electron microscopy of drug-treated N. caninum-infected HFFs demonstrated severe alterations in the parasite cytoplasm, changes in the composition of the matrix of the parasitophorous vacuole (PV) and diminished integrity of the PV membrane. To exert parasiticidal activity, parasites had to be cultured continuously in the presence of 5 μM artemisone or GC007 for 3 weeks. N. caninum tachyzoites readily adapted to a stepwise increase in concentrations (0.5-10 (xM) of GC012, but not to artemisone or GC007. Drugs induced the expression of elevated levels of NcBAG1 and NcSAG4 mRNA, but only NcBAG1 could be detected by immunofluorescence. Thus, artemisinin derivatives represent interesting leads that should be investigated further.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Volume46
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

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Keywords

  • Artemisinin
  • Artemisone
  • Chemotherapy
  • Neospora caninum
  • Resistance
  • Trioxolane

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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