In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts
| Autor: | Mahbubur Rahman, Vera Manser, Vreni Balmer, Pablo Winzer, Andrew Hemphill, Joachim Müller, Richard K. Haynes |
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| Rok vydání: | 2015 |
| Předmět: |
Microbiology (medical)
Cell Survival Antiprotozoal Agents Biology Immunofluorescence Inhibitory Concentration 50 Lactones 03 medical and health sciences Foreskin Microscopy Electron Transmission Parasitic Sensitivity Tests parasitic diseases medicine Humans Parasite hosting Pharmacology (medical) Artemisinin Cells Cultured 030304 developmental biology 0303 health sciences Messenger RNA medicine.diagnostic_test 030306 microbiology Drug Repositioning Neospora Drug Tolerance General Medicine Fibroblasts biology.organism_classification Virology Molecular biology Artemisinins Neospora caninum In vitro 3. Good health Infectious Diseases medicine.anatomical_structure Cytoplasm medicine.drug |
| Zdroj: | International journal of antimicrobial agents |
| ISSN: | 0924-8579 |
| DOI: | 10.1016/j.ijantimicag.2015.02.020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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