IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Psilostachyn C: A sesquiterpene lactone form Ambtosia scabra (Asteraceae) with trypanocidal activity
Autor/es:
SÜLSEN V., FRANK F., CARZOLA C., ANESINI D., PAPADEMETRIO D., ALVAREZ E., MALCHIODI E., MARTINO V AND MUSCHETTI L
Lugar:
London
Reunión:
Congreso; Annual Meeting of the Royal Society of Tropical Medicine and Hygine.; 2008
Institución organizadora:
Royal Society of Tropical Medicine and Hygine
Resumen:
Psilostachyin C: A sesquiterpene lactone from Ambrosia scabra (Asteraceae) with trypanocidal activity   Sülsen V, Frank F, Cazorla S, Anesini C, Malchiodi E,  Papademetrio D, Alvarez E, Martino V  Muschietti L   Chagas´disease is a major health problem in Latin America. The side effects and the emerging resistance to available drugs has led to the urgent need for new therapeutic agents. We have previously reported the antiprotozoal activity of psilostachyin and peruvin from Ambrosia tenuifolia. As a continuation of the ongoing research on plants of the Ambrosia generous, the aim of this study was to isolate trypanocidal compounds from the organic extract of A. scabra by a bioassay-guided fractionation. From the most active fraction against Trypanosoma cruzi epimastigotes (IC50=4.5 mg/ml), a sesquiterpene lactone was isolated and identified as psilosatchyin C. This compound exerted significant in vitro trypanocidal activity against T. cruzi. For epimastigotes IC50 value was 0.64 μg/ml (72 h) while for trypomastigotes 18.87 μg/ml (24 h). Because 50% cytotoxic showed concentration greater than 50 mg/ml on murine T-lymphocytes, we decide to test it in a murine model. Infected mice were treated (1mg/Kg/day) for 5 days founding a significant reduction in circulating parasites compared to untreated one (7.4±1.2x105 vs 1.3±1.8x106 parasites/ml at the peak of parasitemia). Furthermore, studying the way of action of the compound we could demonstrate that psilostachyin C is able to induce apoptosis in a  doses dependent manner. According to these results psilostachyin C may be considered as a candidate molecule for the design of novel trypanocidal agents.