(E)-Piplartine Isolated from Piper pseudoarboreum, a Lead Compound against Leishmaniasis.

Juan C. Ticona,Francisco Bolás-Fernández,Ninoska Flores,Ignacio A. Jiménez,M. Auxiliadora Dea-Ayuela,Pablo Bilbao-Ramos,Isabel L. Bazzocchi

doi:10.3390/foods9091250

Abstract

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.

Highlights

IntroductionLeishmaniases are endemic in large areas of the tropics, subtropics, and the Mediterranean basin, and are among the major neglected tropical diseases causing morbidity worldwide
Leishmaniases are neglected tropical diseases caused by the infection with Leishmania parasites, and are transmitted by the bite of a sand fly belonging to the genera Lutzomyia and Phlebotomus.Leishmaniases are endemic in large areas of the tropics, subtropics, and the Mediterranean basin, and are among the major neglected tropical diseases causing morbidity worldwide
Cutaneous leishmaniasis (CL) is mainly caused by Leishmania major in the Old World and by L. amazonensis and

Summary

Introduction

Leishmaniases are endemic in large areas of the tropics, subtropics, and the Mediterranean basin, and are among the major neglected tropical diseases causing morbidity worldwide. It has broken out of its traditional boundaries and has been reported in new geographic locations with atypical disease manifestations involving novel parasite variants. In spite of the high prevalence, and advances in the chemotherapy for leishmaniasis, the current available drugs, including pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine are compromised by the emergence of resistance, variable sensitivity between species, adverse side effects, requirements for long courses of administration, and high cost [2]. These drawbacks and the absence of vaccines underline the urgent need for searching alternative treatments with acceptable efficacy and safety profile

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Conclusion