Activity of Estafietin and Analogues on Trypanosoma cruzi and Leishmania braziliensis

SÜLSEN, VALERIA; LIZARRAGA, EMILIO; ELSO, ORLANDO; CERNY, NATACHA; SANCHEZ ALBERTI, ANDRÉS; BIVONA, AUGUSTO; MALCHIODI, EMILIO; CAZORLA, SILVIA; CATALÁN, CÉSAR

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2019 vol. 24

1420-3049

Sesquiterpene lactones are naturally occurring compounds mainly found in theAsteraceae 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):11H,13-dihydroestafietin (2), epoxyestafietin (3a and 3b), 11H,13-methoxyestafietin, (4) and11H,13-cianoestafietin. The antiprotozoal activity against Trypanosoma cruzi and Leishmaniabraziliensis of these compounds was evaluated. Epoxyestafietin was the most active compoundagainst T. cruzi trypomastigotes and amastigotes (IC50 values of 18.7 and 2.0 g/mL, respectively).Estafietin (1) and 11H,13-dihydroestafietin (2) were the most active and selective compounds onL. braziliensis promastigotes (IC50 values of 1.0 and 1.3 g/mL, respectively). The antiparasitic activitydemonstrated by estafietin and some of its derivatives make them promising candidates for thedevelopment of effective compounds for the treatment of Chagas disease and leihsmaniasis.