Antiprotozoal compounds from Mikania periplocifolia (Asteraceae)

Abstract

Chagas disease, African trypanosomiasis and Leishmaniasis are neglected parasitic diseases which affect millions of people worldwide. In a previous work, we report the antiprotozoal activity of the dichloromethane extract of Mikania periplocifolia Hook. & Arn. (Asteraceae). The aim of this work was to isolate and identify the bioactive compounds present in the extract. The fractionation of the dichloromethane extract has led to the isolation of the sesquiterpene lactone miscandenin and the flavonoid onopordin, together with the sesquiterpene lactones mikanolide, dihydromikanolide and deoxymikanolide, which have previously shown antiprotozoal activity. Miscandenin and onopordin were assayed in vitro against Trypanosoma cruzi, T. brucei and Leishmania braziliensis. Miscandenin was active against T. cruzi trypomastigotes and amastigotes with IC₅₀ values of 9.1 and 7.7 μg/ml, respectively. This sesquiterpene lactone and the flavonoid onopordin showed activity against T. brucei trypomastigotes (IC₅₀ = 0.16 and 0.37 μg/ml) and L. braziliensis promastigotes (IC₅₀ = 0.6 and 1.2 μg/ml), respectively. The CC₅₀ values on mammalian cells were 37.9 and 53.4 μg/ml for miscandenin and onopordin, respectively. Besides, the pharmacokinetic and physicochemical properties of miscandenin were assessed in silico, showing a good drug-likeness profile. Our results highlight this compound as a promising candidate for further preclinical studies in the search of new drugs for the treatment of trypanosomiasis and leishmaniasis.

Keywords: Asteraceae; Flavonoids; Leishmania sp.; Mikania periplocifolia; Sesquiterpene lactones; Trypanosoma spp..