Browsing by Autor "Pablo Bilbao-Ramos"

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An unprecedented chlorine-containing piperamide from Piper pseudoarboreum as potential leishmanicidal agent
(Elsevier BV, 2019) Ninoska Flores; Juan C. Ticona; Pablo Bilbao-Ramos; María Auxiliadora Dea‐Ayuela; Juan Celidonio Ruiz Macedo; Isabel L. Bazzocchi; F. Bolás‐Fernández; Ignacio A. Jiménez
(E)-Piplartine Isolated from Piper pseudoarboreum, a Lead Compound against Leishmaniasis
(Multidisciplinary Digital Publishing Institute, 2020) Juan C. Ticona; Pablo Bilbao-Ramos; Ninoska Flores; María Auxiliadora Dea‐Ayuela; F. Bolás‐Fernández; Ignacio A. Jiménez; Isabel L. Bazzocchi
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.
Flavonoids from Piper Species as Promising Antiprotozoal Agents against Giardia intestinalis: Structure-Activity Relationship and Drug-Likeness Studies
(Multidisciplinary Digital Publishing Institute, 2022) Juan C. Ticona; Pablo Bilbao-Ramos; Ángel Amesty; Ninoska Flores; María Auxiliadora Dea‐Ayuela; Isabel L. Bazzocchi; Ignacio A. Jiménez
Diarrhea diseases caused by the intestinal protozoan parasite Giardia intestinalis are a major global health burden. Moreover, there is an ongoing need for novel anti-Giardia drugs due to drawbacks with currently available treatments. This paper reports on the isolation and structural elucidation of six new flavonoids (1-6), along with twenty-three known ones (7-29) from the Piper species. Their structures were established by spectroscopic and spectrometric techniques. Flavonoids were tested for in vitro antiprotozoal activity against Giardia intestinalis trophozoites. In addition, structure-activity relationship (SAR) and in silico ADME studies were performed to understand the pharmacophore and pharmacokinetic properties of these natural compounds. Eight flavonoids from this series exhibited remarkable activity in the micromolar range. Moreover, compound 4 was identified as having a 40-fold greater antiparasitic effect (IC50 61.0 nM) than the clinical reference drug, metronidazole (IC50 2.5 µM). This antiprotozoal potency was coupled with an excellent selectivity index (SI 233) on murine macrophages and in silico drug-likeness. SAR studies revealed that the substitution patterns, type of functional group, and flavonoid skeleton played an essential role in the activity. These findings highlight flavonoid 4 as a promising candidate to develop new drugs for the treatment of Giardia infections.
Leishmaniasis in the major endemic region of Plurinational State of Bolivia: Species identification, phylogeography and drug susceptibility implications
(Elsevier BV, 2017) Pablo Bilbao-Ramos; María Auxiliadora Dea‐Ayuela; Oscar Victor Cardenas-Alegría; Efraín Salamanca; José Antonio Santalla-Vargas; C. Benito; Ninoska Flores; F. Bolás‐Fernández