title: In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii.
abstract: BACKGROUND
  Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS), or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite.
  
  
  METHODS
  LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software.
  
  
  RESULTS
  Artesunate showed a mean tachyzoite inhibitory concentration (IC50) of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites.
  
  
  CONCLUSIONS
  Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.
authors.affiliation: Laboratório de Parasitologia Médica, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, SP, Brasil. thaiscobellis@bol.com.br
authors.forename: Thaís Cobellis
authors.initials: TC
authors.lastname: Gomes
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade Júnior
authors.forename: Susana Angélica Zevallos
authors.initials: SA
authors.lastname: Lescano
authors.forename: Vicente
authors.initials: V
authors.lastname: Amato-Neto
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D000977:Antiparasitic Agents; D037621:Artemisinins; D000077332:Artesunate