Browsing by Autor "Isabel L. Bazzocchi"

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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
Antiparasitic activity of flavonoids from Piper species
(Thieme Medical Publishers (Germany), 2010) Juan C. Ticona; N Flores; David Gutiérrez; A. Giménez; Ignacio A. Jiménez; Isabel L. Bazzocchi
Parasitic diseases, including leishmaniasis, chagas and malaria, are serious problems for public health throughout the world, especially in tropical and subtropical regions [1]. Due to the absence of effective vaccines, inadequate chemotherapy and the emergence of drug resistance, currently, there is an urgent need to search for novel, effective and safe drugs for the treatment of these diseases [2]. Several Piper species have been used in the traditional medicine in Latin America, including for the treatment of parasitic diseases [3]. As part of our research aiming to uncover antiparasitic compounds from Bolivian Piper species, we studied the dichloromethane extract from the leaves of Piper aduncum, P. acutifolium, P. glabratum, P. heterophyllum, P. pilliraneum and P. rusbyi. This study has led to the isolation of eight known flavonoids and a new compound, 5,5′-dihydroxy-7,3′-dimethoxy-flavanone. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC and HMBC). In the search for new antiparasitic agents, these compounds were evaluated in vitro against three strains of Leishmania (L. amazonensis, L. braziliensis and L. donovani), Trypanosoma cruzi and Plasmodium falciparum. 4′,7-Dimethoxy-5-hydroxy-flavanone (IC50 4.0µg/mL) showed a moderate activity against P. falciparum. The most active compound against promastigote forms of the three Leishmania strains was flavokavain B (IC50 5.4µg/mL), with twice the activity of the control pentamidine (IC50 10.0µg/mL). These results support the use of Piper species as a traditional remedy in the treatment of parasitic diseases.
Antiparasitic activity of prenylated benzoic acid derivatives from Piper species
(Elsevier BV, 2009) Ninoska Flores; Ignacio A. Jiménez; Alberto Giménez; Grace Ruiz; David Gutiérrez; Geneviève Bourdy; Isabel L. Bazzocchi
Antiplasmodial activity of amides and amines from Withania aristata, an endemic species of the Canary islands
(Thieme Medical Publishers (Germany), 2010) GG Llanos; Oliver Callies; David Gutiérrez; N Flores; Ignacio A. Jiménez; A. Giménez; Isabel L. Bazzocchi
Malaria continues to be a major health challenge in most tropical and subtropical regions. The most severe form of human malaria is caused by Plasmodium falciparum, responsible for more than one million deaths per year. Due to the emergence and spread of drug resistance to the available antiplasmodial drugs, its treatment has become a serious problem. Therefore, new molecules with novel mechanisms of action are required [1]. In this context, natural products can deliver new lead compounds for more effective drugs than those currently in clinical use [2]. As part of our research for bioactive metabolites from natural sources, Withania aristata (Aiton) Pauquy (Solanaceae), an endemic species of the Canary Islands used in folk medicine, was studied. The phytochemical analysis of the dichloromethane extract from the leaves of this plant led to the isolation of 3 amide and 6 amine type metabolites, two of them, 2-(4-hydroxy-3,5-dimethoxyphenyl)-3-oxetanamine and N-4-(3-furoylamine)-1-butanol, not previously reported. Their structures were determined by means of spectroscopic studies, including 1D and 2D NMR experiments. The antiplasmodial activity of the compounds was evaluated against a strain of Plasmodium falciparum (F-32 Tanzania). N-cis-feruloyltyramine and 4-O-methyldopamine showed moderate activity (IC50 4.2 and 3.0µg/mL, respectively), whereas the activity of the most potent compound, N-cis-p-coumaroyltyramine, was comparable to that of the control chloroquine (IC50 0.7 and 0.1µg/mL, respectively). A preliminary structure-activity relationship study indicated that the configuration of the double bond in the amides and the regiosubstitution of the aromatic ring in the amines play an important role in the activity.
Benzoic Acid Derivatives from Piper Species and Their Antiparasitic Activity
(American Chemical Society, 2008) Ninoska Flores; Ignacio A. Jiménez; Alberto Giménez; Grace Ruiz; David Gutiérrez; Geneviève Bourdy; Isabel L. Bazzocchi
Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively.
(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 delineatum modulate quorum-sensing-regulated phenotypes in Vibrio harveyi
(Elsevier BV, 2015) Alberto J. Martín‐Rodríguez; Juan C. Ticona; Ignacio A. Jiménez; Ninoska Flores; José J. Fernández; Isabel L. Bazzocchi
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.
Leishmanicidal Constituents from the Leaves of Piper rusbyi
(Thieme Medical Publishers (Germany), 2007) Ninoska Flores; Gabriela M. Cabrera; Ignacio A. Jiménez; José E. Piñero; Alberto Giménez; Geneviève Bourdy; Fernando Cortés-Selva; Isabel L. Bazzocchi
The kavapyrone (+)-(7 R,8 S)-epoxy-5,6-didehydrokavain (1) and the chalcone flavokavain B (2) were isolated from Piper rusbyi as the bioactive components by bioassay-guided fractionation, using an in vitro assay against promastigote forms of three Leishmania strains. In addition, the new kavapyrone, (7 R,8 R/7 S,8 S)-dihydroxy-5,6-didehydrokavain (3), which is very likely an artifact, and four known compounds (4-7) were isolated. Their structures were elucidated on the basis of spectral analysis, and the absolute configurations of compounds 1 and 3 were established by CD studies and the modified Mosher ester procedure, respectively. All compounds were evaluated for in vitro leishmanicidal activity. The most active compounds 1 (IC50=81.9 microM) and 2 (IC50=11.2 microM) were also evaluated in vivo against a New World strain of cutaneous leishmaniasis, and the results showed the efficacy of 2 at a dose of 5 mg/kg/day. Compounds 1 and 3 were also assayed as reversal agents against a multidrug-resistant Leishmania tropica line, but were found to be inactive.