DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Nanoemulsion composed of 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol), a synthetic analog of 3-alkylpiridine marine alkaloid : development, characterization, and antimalarial activity.(2020) Silva, Marina Goulart da; Cardoso, Jéssica Ferreira; Perasoli, Fernanda Barçante; Branquinho, Renata Tupinambá; Mourão, Renata Silva; Tavares, Harley da Silva; Xocaira, Maria Luiza Costa Trench; Guimarães, Daniel Silqueira Martins; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla; Silva, Gisele Rodrigues daMalaria treatment is based on a reduced number of antimalarial drugs, and drug resistance has emerged, leading to the search for new antimalarial drugs incorporated into pharmaceutical formulations. In this study, 10-(4,5- dihydrothiazol-2-yl)thio)decan-1-ol) (thiazoline), a synthetic analog of 3-alkylpiridine marine alkaloid, and a potent antimalarial substance, was incorporated into O/W nanoemulsion. This formulation was prepared by a 23 factorial design. It was characterized by globule diameter, polydispersity index, zeta potential, encapsulation efficiency, in vitro thiazoline release at pH 2 and 6.86, and accelerated stability. In vitro and in vivo antimalarial activity was determined against P. falciparum and P. berghei, respectively. Thiazoline nanoemulsion showed 248.8 nm of globule diameter, 0.236 of polydispersity index, -38.5 mV of zeta potential, 96.92% encapsulation efficiency, and it was stable for 6 months. Thiazoline release profiles differed in acidic and neutral media, but in both cases, the nanoemulsion controlled and prolonged the thiazoline delivery. Thiazoline nanoemulsion exerted in vitro antimalarial activity against the parasite (IC50 = 1.32 µM), and it significantly reduced the in vivo parasitemia for 8 days without increasing the survival time of animals. Therefore, the thiazoline nanoemulsion represents a strategy to treat malaria combining an antimalarial candidate and a new nanocarrier.Item Extraction and fractionation effects on antiplasmodial activity and phytochemical composition of Palicourea hoffmannseggiana(2021) Ohashi, Leticia Hiromi; Gontijo, Douglas da Costa; Nascimento, Maria Fernanda Alves do; Margalho, Luciano Ferreira; Brandão, Geraldo Célio; Oliveira, Alaíde Braga deThe present study on Palicourea hoffmannseggiana, which was collected at Marapanim, state of Pará, Brazil, comprises the preparation of different stem and leaf extracts and fractions. Ethanol, hydroethanol, and water extracts were prepared by several methods and evaluated for in vitro activity against resistant Plasmodium falciparum (W2 strain), disclosing a low parasite growth inhibition effect ( < 50 %). Dereplication by UPLC-DAD-ESI −MS of the leaf ethanol extract showed the presence of two known alkaloids, lyalosidic and strictosidinic acids, along with a sinapoyl ester of lyalosidic acid, with m/z 719.33 [M +H] + , which is possibly a new monoterpene indole alkaloid representative. Sequential liquid-liquid acid-base alkaloid separations from the leaf ethanol extract as well as directly from leaf powder afforded fractions of increased parasite growth inhibition, reaching up to 92.5±0.7%. The most bioactive fractions were shown to contain the β-carboline alkaloids harmane and 4-methyl-β-carboline, along with N-methyl-tryptamine and N-acetyl-tryptamine, while monoterpene indole alkaloids were detected in inactive fractions of these processes. The present results demonstrate that these preliminary fractionation methods can lead to significantly active fractions supporting an adequate scale-up to carrying out the isolation of anti-plasmodial compounds.Item Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle : mode of action, mutagenicity profile, and Caco-2 cell-based permeability.(2019) Guimarães, Daniel Silqueira Martins; Luz, Letícia Silveira de Sousa; Nascimento, Sara Batista do; Silva, Lorena Rabelo; Martins, Natália Rezende de Miranda; Almeida, Heloísa Gonçalves de; Reis, Vitória de Souza; Maluf, Sarah El Chamy; Budu, Alexandre; Marinho, Juliane Aparecida; Abramo, Clarice; Carmona, Adriana Karaoglanovic; Silva, Marina Goulart da; Silva, Gisele Rodrigues da; Kemmer, Victor Matheus; Butera, Anna Paola; Viana, Renato Márcio Ribeiro; Gazarini, Marcos Leoni; Nascimento Júnior, Clébio Soares; Guimarães, Luciana; Santos, Fabio Vieira dos; Castro, Whocely Victor de; Ribeiro, Gustavo Henrique; Brito, Cristiana Ferreira Alves de; Varotti, Fernando de PillaThe development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV–vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.Item Bioprospection for antiplasmodial activity, and identification of bioactive metabolites of native plants species from the Mata Atlântica biome, Brazil.(2019) Gontijo, Douglas da Costa; Leite, João Paulo Viana; Nascimento, Maria Fernanda Alves do; Brandão, Geraldo Célio; Oliveira, Alaíde Braga deA total of 33 extracts of eleven different plants species from Mata Atlântica biome, Brazil, and different fractions of the bioactive extracts were evaluated against chloroquine-resistant Plasmodium falciparum W2 strain by PfLDH method and cytotoxicity to HepG2 cells by the MTT assay, and chemically characterized by LC-DAD-ESI-MS/MS analysis. The results allowed the identification of Alchornea glandulosa, Miconia latecrenata, and Psychotria suterella as the most active plant species. Different flavonoids and tannins in Alchornea glandulosa and Miconia latecrenata besides alkaloids in Psychotria suterella were identified. Bioguided fractionation of A. glandulosa and M. latecrenata leaves extracts led to fractions exhibiting high parasite growth inhibition. Seven known alkaloids were identified in the P. suterella extract, and of these, only 5-carboxystrictosidine had been assayed for antiplasmodial activity what points to this species as the most promising among the eleven one assayed.Item In vitro antiplasmodial activity and identification, using tandem LC-MS, of alkaloids from Aspidosperma excelsum, a plant used to treat malaria in Amazonia.(2019) Nascimento, Myrth Soares do; Pina, Nayla di Paula Vieira; Silva, Andressa Santa Brigida da; Gomes, Luís Fabio dos Santos; Vasconcellos, Flávio de; Brandão, Geraldo Célio; Nascimento, Maria Fernanda Alves do; Oliveira, Alaide Braga de; Barbosa, Wagner Luiz RamosEthnopharmacological relevance: Aspidosperma excelsum Benth. (Apocynaceae), a native tree in the Brazilian Amazonia, is traditionally used to treat various diseases, including malaria. Aim of study: To investigate the chemical constitution, antiplasmodial activity and cytotoxicity of samples obtained from A. excelsum trunk bark by different procedures aiming to evaluate their potential as an antimalarial phytomedicine. Materials and methods: A hydroethanolic extract and alkaloid extracts were prepared and assayed for antiplasmodial activity and cytotoxicity against chloroquine-resistant Plasmodium falciparum (W2 strain) and HepG2 cells, respectively. Taking into account the known occurrence and antimalarial activity of Aspidosperma monoterpene indole alkaloids (MIA), acid-base extractions were carried out and the fractions were assayed for antiplasmodial activity and cytotoxicity. All the samples were analysed by hyphenated chromatographic techniques, such as UPLC-DAD-ESI-MS/MS and HRMS (HPLC-MS MicroTOF), comparing their chemical composition to the literature data. Results: The hydroethanolic extract disclosed a moderate in vitro activity against chloroquine-resistant Plasmodium falciparum (W2 strain) with IC50 23.68 ± 3.08 µg/mL), low cytotoxicity to HepG2 cells (> 250 µg/ mL) and good SI (> 10.56). A total of 20 known monoterpene indole alkaloids were identified, seven of which are here firstly described for A. excelsum. Known highly active alkaloids, namely demethylaspidospermine, aspidocarpine, and ochrolifuanine are present in active alkaloid fractions and might contribute to their observed antiplasmodial effect. An alkaloid fraction (Ae-Alk2), obtained directly from trunk bark by extraction with dil. aqueous HCl, pointed out for its activity (IC50 8.75 ± 2.26 µg/mL, CC50 185.14 ± 1.97 µg/mL, SI 21.16) and should be highlighted as the most promising out of the assayed samples. Conclusion: The present results represent a preliminary support to the alleged antimalarial use of A. excelsum trunk bark and allowed to highlight alkaloid fractions as promising phytomedicines.Item 7-Chloroquinolinotriazoles : synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies.(2014) Pereira, Guilherme Rocha; Brandão, Geraldo Célio; Arantes, Lucas Micquéias; Oliveira Junior, Haliton Alves de; Paula, Renata Cristina de; Nascimento, Maria Fernanda Alves do; Santos, Fábio Mendes dos; Rocha, Ramon Kleber da; Lopes, Júlio César Dias; Oliveira, Alaíde Braga deTwenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between 4-azido-7- chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 mM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 mM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained.