Activity of Estafietin and Analogues on <i>Trypanosoma cruzi</i> and <i>Leishmania braziliensis</i>
Valeria P. Sülsen,
Emilio F. Lizarraga,
Orlando G. Elso,
Natacha Cerny,
Andrés Sanchez Alberti,
Augusto E. Bivona,
Emilio L. Malchiodi,
Silvia I. Cazorla,
César A. N. Catalán
Affiliations
Valeria P. Sülsen
CONICET—Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Junín 956 2° floor, Buenos Aires 1113, Argentina
Emilio F. Lizarraga
Instituto de Fisiología Animal, Fundación Miguel Lillo and Facultad de Ciencias Naturales e Instituto Miguel Lillo, Universidad Nacional de Tucumán, Tucumán T4000INI, Argentina
Orlando G. Elso
CONICET—Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), Junín 956 2° floor, Buenos Aires 1113, Argentina
Natacha Cerny
CONICET—Universidad Nacional de Luján, Instituto de Ecología y Desarrollo Sustentable (INEDES), Ruta 5 y Avenida Constitución, Luján 6700, Argentina
Andrés Sanchez Alberti
Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, Argentina
Augusto E. Bivona
Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, Argentina
Emilio L. Malchiodi
Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4° floor, Buenos Aires 1113, Argentina
Silvia I. Cazorla
CONICET—Universidad de Buenos Aires, Instituto de Microbiología y Parasitología Médica—CONICET (IMPaM), Facultad de Medicina, Paraguay 2155. 13° floor, Buenos Aires C1121ABG, Argentina
César A. N. Catalán
CONICET—Universidad Nacional de Tucumán, Instituto de Química del Noroeste—CONICET (INQUINOA), Ayacucho 471, San Miguel de Tucumán T4000INI, Argentina
Sesquiterpene lactones are naturally occurring compounds mainly found in the Asteraceae family. These types of plant metabolites display a wide range of biological activities, including antiprotozoal activity and are considered interesting structures for drug discovery. Four derivatives were synthesized from estafietin (1), isolated from Stevia alpina (Asteraceae): 11βH,13-dihydroestafietin (2), epoxyestafietin (3a and 3b), 11βH,13-methoxyestafietin, (4) and 11βH,13-cianoestafietin. The antiprotozoal activity against Trypanosoma cruzi and Leishmania braziliensis of these compounds was evaluated. Epoxyestafietin was the most active compound against T. cruzi trypomastigotes and amastigotes (IC50 values of 18.7 and 2.0 µg/mL, respectively). Estafietin (1) and 11βH,13-dihydroestafietin (2) were the most active and selective compounds on L. braziliensis promastigotes (IC50 values of 1.0 and 1.3 μg/mL, respectively). The antiparasitic activity demonstrated by estafietin and some of its derivatives make them promising candidates for the development of effective compounds for the treatment of Chagas disease and leihsmaniasis.