title: In vitro evaluation of β-carboline alkaloids as potential anti-Toxoplasma agents.
abstract: BACKGROUND
  Toxoplasmosis is a worldwide infection caused by the protozoan parasite Toxoplasma gondii, which causes chorioretinitis and neurological defects in congenitally infected newborns or immunodeficient patients. The efficacy of the current treatment is limited, primarily by serious host toxicity. In recent years, research has focused on the development of new drugs against T. gondii. β-Carbolines (βCs), such as harmane, norharmane and harmine, are a group of naturally occurring alkaloids that show microbicidal activity. In this work, harmane, norharmane and harmine were tested against T. gondii.
  
  
  RESULTS
  The treatment of extracellular tachyzoites with harmane, norharmane and harmine showed a 2.5 to 3.5-fold decrease in the invasion rates at doses of 40 μM (harmane and harmine) and 2.5 μM (norharmane) compared with the untreated parasites. Furthermore, an effect on the replication rate could also be observed with a decrease of 1 (harmane) and 2 (norharmane and harmine) division rounds at doses of 5 to 12.5 μM. In addition, the treated parasites presented either delayed or no monolayer lysis compared with the untreated parasites.
  
  
  CONCLUSIONS
  The three βC alkaloids studied (norharmane, harmane and harmine) exhibit anti-T. gondii effects as evidenced by the partial inhibition of parasite invasion and replication. A dose-response effect was observed at a relatively low drug concentration (< 40 μM), at which no cytotoxic effect was observed on the host cell line (Vero).
authors.affiliation: Laboratorio de Parasitología Molecular, IIB-INTECH, CONICET/UNSAM, Av, Intendente Marino Km, 8,2, C,C 164, (B7130IIWA) Chascomús, Prov, Buenos Aires, Argentina.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Alomar
authors.forename: Federico A O
authors.initials: FA
authors.lastname: Rasse-Suriani
authors.forename: Agustina
authors.initials: A
authors.lastname: Ganuza
authors.forename: Verónica M
authors.initials: VM
authors.lastname: Cóceres
authors.forename: Franco M
authors.initials: FM
authors.lastname: Cabrerizo
authors.forename: Sergio O
authors.initials: SO
authors.lastname: Angel
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development; D014123:Toxoplasmosis / Q000188:drug therapy*
chemical_list: D000470:Alkaloids; D002243:Carbolines