title: Effects of artesunate against Trypanosma cruzi.
abstract: Therapy against Trypanosma cruzi relies on only two chemically related nitro-derivative drugs, benznidazole and nifurtimox, both limited by poor efficacy and toxicity. It is suspected that with prolonged usage of these drugs, resistant parasites will be selected, which results in risk for treatment failure over the time. Herein, we studied the in vitro activity of artesunate, the most effective drug to treat severe P. falciparum and chloroquine-resistant P. vivax, on three strains of T. cruzi originated in different regions of Latin America (Argentina, Nicaragua and Brazil). The results of these assays showed that artesunate inhibits multiplication of epimastigotes (IC50 = 50, 6.10 and 23 µM, respectively) and intracellular amastigotes (IC50 = 15, 0.12 and 6.90 µM, respectively), indicating that it represents a potent anti-T. cruzi compound in terms of inhibiting parasite multiplication in vitro. We then tested the effect of artesunate in Balb/c mice infected with Brazil strain and found that it failed to cure the infection, suggesting that the drug may be unsuitable for in vivo treatment. When infected mice were treated with high doses AS + BZ, the outcome of infection was similar to that observed in mice treated with BZ alone. Nevertheless, understanding of structure-activity relationship of artesunate might lead to the development of new and effective drugs against T. cruzi.
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben", Ave. Paseo Colón 568, Ciudad Autónoma, Buenos Aires ZC 1063, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Gabriela Carina
authors.initials: GC
authors.lastname: Olivera
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben", Ave. Paseo Colón 568, Ciudad Autónoma, Buenos Aires ZC 1063, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben", Ave. Paseo Colón 568, Ciudad Autónoma, Buenos Aires ZC 1063, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: marnatch@yahoo.com.ar.
authors.forename: Mariela Natacha
authors.initials: MN
authors.lastname: González
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D014355:Chagas Disease / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D005260:Female; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D037621:Artemisinins; D014344:Trypanocidal Agents; D000077332:Artesunate
keywords: Artesunate; Chagas disease; Chemotherapy; Trypanosma cruzi