(E)-Piplartine Isolated From Piper Pseudoarboreum, A Lead Compound Against Leishmaniasis

The current therapies of leishmaniasis, the second most widespread neglected tropical disease, have limited effectiveness and toxic side effects. In this regard, natural products play an important role in overcoming the current need for new leishmanicidal agents. The present study reports a bioassay-guided fractionation of the ethanolic extract of leaves ofPiper pseudoarboreumagainst four species ofLeishmaniaspp. promastigote forms, which afforded six known alkamides (1-6). Their structures were established on the basis of spectroscopic and spectrometric analysis. Compounds 2 and 3were identified as the most promising ones, displaying higher potency against Leishmaniaspp. promastigotes (IC(50)values ranging from 1.6 to 3.8 mu M) and amastigotes ofL. amazonensis(IC50 values ranging from 8.2 to 9.1 mu M) than the reference drug, miltefosine. The efficacy of (E)-piplartine (3) againstL. amazonensisinfection in an in vivo model for cutaneous leishmaniasis was evidenced by a significant reduction of the lesion size footpad and spleen parasite burden, similar to those of glucantime used as the reference drug. This study reinforces the therapeutic potential of (E)-piplartine as a promising lead compound against neglected infectious diseases caused byLeishmaniaparasites.