OBJECTIVES: To study the effect of aureobasidin A, an inhibitor of inositol phosphorylceramide (IPC) synthase, on Leishmania growth and infectivity. METHODS: Effects of aureobasidin A were determined for: (i) promastigote growth in axenic culture; (ii) promastigote infectivity in macrophage monolayers; (iii) development of footpad lesions in BALB/c mice; (iv) differentiation of amastigotes into promastigotes. RESULTS: Aureobasidin A (20 microM) inhibited 90% of Leishmania (Leishmania) amazonensis promastigote growth in axenic culture, but the parasites remained viable, i.e. growth curves returned to normal after aureobasidin A was removed from culture medium. The aureobasidin A IC50 was determined by MTT assay as 4.1 microM for L. (L.) amazonensis promastigotes, 12.6 microM for Leishmania (Leishmania) major and 13.7 microM for Leishmania (Viannia) braziliensis. There was a significant delay in infection when L. (L.) amazonensis promastigotes pre-treated with aureobasidin A were inoculated into BALB/c mouse footpads. When aureobasidin A was added to cultured macrophages infected with amastigotes, the number of infected macrophages was reduced by >90%. CONCLUSIONS: Aureobasidin A is an interesting pharmacological tool to investigate the effect of lipid metabolism inhibition in Leishmania spp.
OBJECTIVES: To study the effect of aureobasidin A, an inhibitor of inositol phosphorylceramide (IPC) synthase, on Leishmania growth and infectivity. METHODS: Effects of aureobasidin A were determined for: (i) promastigote growth in axenic culture; (ii) promastigote infectivity in macrophage monolayers; (iii) development of footpad lesions in BALB/c mice; (iv) differentiation of amastigotes into promastigotes. RESULTS:Aureobasidin A (20 microM) inhibited 90% of Leishmania (Leishmania) amazonensis promastigote growth in axenic culture, but the parasites remained viable, i.e. growth curves returned to normal after aureobasidin A was removed from culture medium. The aureobasidin A IC50 was determined by MTT assay as 4.1 microM for L. (L.) amazonensis promastigotes, 12.6 microM for Leishmania (Leishmania) major and 13.7 microM for Leishmania (Viannia) braziliensis. There was a significant delay in infection when L. (L.) amazonensis promastigotes pre-treated with aureobasidin A were inoculated into BALB/c mouse footpads. When aureobasidin A was added to cultured macrophages infected with amastigotes, the number of infected macrophages was reduced by >90%. CONCLUSIONS:Aureobasidin A is an interesting pharmacological tool to investigate the effect of lipid metabolism inhibition in Leishmania spp.
Authors: Carolina de Siqueira Paladi; Isabella Aparecida Salerno Pimentel; Simone Katz; Rodrigo L O R Cunha; Wagner Alves de Souza Judice; Antonio C F Caires; Clara Lúcia Barbiéri Journal: PLoS Negl Trop Dis Date: 2012-05-15
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Authors: Carolina B Moraes; Gesa Witt; Maria Kuzikov; Bernhard Ellinger; Theodora Calogeropoulou; Kyriakos C Prousis; Stefano Mangani; Flavio Di Pisa; Giacomo Landi; Lucia Dello Iacono; Cecilia Pozzi; Lucio H Freitas-Junior; Bruno Dos Santos Pascoalino; Claudia P Bertolacini; Birte Behrens; Oliver Keminer; Jennifer Leu; Markus Wolf; Jeanette Reinshagen; Anabela Cordeiro-da-Silva; Nuno Santarem; Alberto Venturelli; Stephen Wrigley; Deepa Karunakaran; Bethlehem Kebede; Ina Pöhner; Wolfgang Müller; Joanna Panecka-Hofman; Rebecca C Wade; Martina Fenske; Joachim Clos; José María Alunda; María Jesús Corral; Elisa Uliassi; Maria Laura Bolognesi; Pasquale Linciano; Antonio Quotadamo; Stefania Ferrari; Matteo Santucci; Chiara Borsari; Maria Paola Costi; Sheraz Gul Journal: SLAS Discov Date: 2019-03 Impact factor: 3.341