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

Müller, Joachim; Balmer, Vreni; Winzer, Pablo Arnold; Rahman, Mahbubur; Manser, Vera; Haynes, Richard K; Hemphill, Andrew (2015). In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts. International journal of antimicrobial agents, 46(1), pp. 88-93. Elsevier 10.1016/j.ijantimicag.2015.02.020

Text Müller et al., 2015 IJAA.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB) | Request a copy

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 3-54nM), 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 5μM artemisone or GC007 for 3 weeks. N. caninum tachyzoites readily adapted to a stepwise increase in concentrations (0.5-10μM) 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.

Interest & Impact

Downloads

2 since deposited on 17 Jun 2016
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item