title: In vitro susceptibility of Trypanosoma cruzi strains from Santander, Colombia, to hexadecylphosphocholine (miltefosine), nifurtimox and benznidazole.
abstract: BACKGROUND
  The current chemotherapy for Chagas disease is unsatisfactory with only two drugs available for treatment. Research to discover new drugs for Chagas disease is urgent. Hexadecyl-phosphocholine (HPC, miltefosine) has been demonstrated to have in vitro activity against Trypanosoma cruzi parasites, but its activity on different Colombian T. cruzi strains is not known.
  
  
  OBJECTIVE
  To evaluate the in vitro susceptibility of T. cruzi strains isolated from humans and vectors in Santander, Colombia. to miltefosine, nifurtimox and benznidazole.
  
  
  METHODS
  Eight T. cruzi Colombian strains and three reference strains (Esmeraldo, SilvioX10 and Y) were studied. Drug activities against extracellular epimastigotes and intracellular amastigotes were determined by microscopic counting. The results were expressed as the concentrations that inhibited 50% and 90% growth (IC50 and IC90).
  
  
  RESULTS
  For miltefosine a similar range of drug activity was observed against all the Colombian strains, all parasites being more susceptible to miltefosine than to the reference drugs. The intracellular amastigotes were more susceptible to miltefosine (IC50 0.08 to 0.63 microM and IC90 0.21 to 2.21 microM) than extracellular forms (IC50 <0.92 to 2.29 microM and IC90 1.38 to 4.76 microM). For reference drugs, parasites were more susceptible to nifurtimox than to benznidazole and some differences in activity of benznidazole between T. cruzi strains was observed.
  
  
  CONCLUSIONS
  The results showed the significant in vitro activity of miltefosine against T. cruzi stages, and the expected results for the reference drugs. Further in vivo studies with miltefosine are planned.
authors.affiliation: Centro de Investigación en Enfermedades Tropicales, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Colombia.
authors.forename: Katherine Paola
authors.initials: KP
authors.lastname: Luna
authors.forename: Indira Paola
authors.initials: IP
authors.lastname: Hernández
authors.forename: César Mauricio
authors.initials: CM
authors.lastname: Rueda
authors.forename: María Magdalena
authors.initials: MM
authors.lastname: Zorro
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
authors.forename: Patricia
authors.initials: P
authors.lastname: Escobar
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003105:Colombia; D009547:Nifurtimox / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; D010767:Phosphorylcholine; C039128:miltefosine; D009547:Nifurtimox; C009999:benzonidazole