Anti-malarial, anti-trypanosomal, and anti-leishmanialactivities of jacaranone isolated from Pentacalia desiderabilis(Vell.) Cuatrec. (Asteraceae)

ABSTRACT

Leishmaniasis, Chagas disease, and malaria affectthe poorest population around the world, with an elevatedmortality and morbidity. In addition, the therapeutic alternativesare usually toxic or ineffective drugs especially thoseagainst the trypanosomatids. In the course of selection of newanti-protozoal compounds from Brazilian flora, the CH2Cl2phase from MeOH extract obtained from the leaves ofPentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae)showed in vitro anti-leishmanial, anti-malarial, and antitrypanosomalactivities. The chromatographic fractionationof the CH2Cl2 phase led to the isolation of thebioactive compound, which was characterized as jacaranone[methyl (1-hydroxy-4-oxo-2,5-cyclohexandienyl)acetate], by spectroscopic methods. This compoundshowed activity against promastigotes of Leishmania (L.)chagasi, Leishmania (V.) braziliensis, and Leishmania(L.). amazonensis showing an IC50 of 17.22, 12.93, and11.86 μg/mL, respectively. Jacaranone was also tested invitro against the Trypanosoma cruzi trypomastigotes andPlasmodium falciparum chloroquine-resistant parasites(K1 strain) showing an IC50 of 13 and 7.82 μg/mL,respectively, and was 3.5-fold more effective than benznidazolein anti-Trypanosoma cruzi assay. However, despiteof the potential against promatigotes forms, this compoundwas not effective against amastigotes of L. (L.) chagasiand T. cruzi. The cytotoxicity study using Kidney Rhesusmonkey cells, demonstrated that jacaranone showedselectivity against P. falciparum (21.75 μg/mL) and aselectivity index of 3. The obtained results suggested thatjacaranone, as other similar secondary metabolites orsynthetic analogs, might be useful tolls for drug designfor in vivo studies against protozoan diseases...