(<i>E</i>)-Piplartine Isolated from <i>Piper pseudoarboreum</i>, a Lead Compound against <i>Leishmaniasis</i>
Juan C. Ticona,
Pablo Bilbao-Ramos,
Ninoska Flores,
M. Auxiliadora Dea-Ayuela,
Francisco Bolás-Fernández,
Ignacio A. Jiménez,
Isabel L. Bazzocchi
Affiliations
Juan C. Ticona
Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain
Pablo Bilbao-Ramos
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
Ninoska Flores
Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Avenida Saavedra 2224, Miraflores, La Paz, Bolivia
M. Auxiliadora Dea-Ayuela
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
Francisco Bolás-Fernández
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
Ignacio A. Jiménez
Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain
Isabel L. Bazzocchi
Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain
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.
