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 of Piper pseudoarboreum against four species of Leishmania spp. promastigote forms, which afforded six known alkamides (1-6). Their structures were established on the basis of spectroscopic and spectrometric analysis. Compounds 2 and 3 were identified as the most promising ones, displaying higher potency against Leishmania spp. promastigotes (IC50 values ranging from 1.6 to 3.8 µM) and amastigotes of L. amazonensis (IC50 values ranging from 8.2 to 9.1 µM) than the reference drug, miltefosine. The efficacy of (E)-piplartine (3) against L. amazonensis infection 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 by Leishmania parasites.
Bibliographical noteFunding Information:
Funding: This research was funded by RTI2018-094356-B-C21 Spanish MINECO project, cofunded by the European Regional Development Fund (FEDER) and PCI-Iberoamerica A/030160/10 and AP/039767/11 projects from Spanish MAEC-AECID. J.C.T. and P.B.-R. are grateful to Spanish MAEC-AECID for their fellowships.
© 2020 by the authors.
- Bioassay-guided fractionation
- Leishmanicidal activity
- Piper pseudoarboreum