Browsing by Author "Nascimento, Maria Fernanda Alves do"

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    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 de
    Twenty-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.
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    Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS.
    (2019) Gontijo, Douglas da Costa; Brandão, Geraldo Célio; Nascimento, Maria Fernanda Alves do; Oliveira, Alaide Braga de
    Objectives: To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. Methods: Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. Key findings: Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 3.0% growth inhibition at 50 lg/ml and CC50 72.1 5.1 lg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O-methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 2.7 lg/ml, CC50 38.3 2.3 lg/ml, SI 1.6) while O-methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 1.9% growth inhibition at 50 lg/ml, CC50 274.4 0.5 lg/ml). Conclusions: Characterization of Xylopia sericea leaves ethanol extract by UPLCDAD-ESI-MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O-methylmoschatoline in this Xylopia species are reported by the first time.
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    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 de
    A 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.
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    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 de
    The 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.
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    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 Ramos
    Ethnopharmacological 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.
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    Phytochemistry and antiplasmodial activity of Xylopia sericea leaves.
    (2019) Gontijo, Douglas da Costa; Nascimento, Maria Fernanda Alves do; Brandão, Geraldo Célio; Oliveira, Alaide Braga de
    Aiming to investigate the antiplasmodial activity and the phytochemical composition of Xylopia sericea leaves, the essential oil and dichloromethane extract were analyzed by gas and liquid chromatography, respectively, both of them coupled to mass spectrometry, and were evaluated against the chloroquine-resistant Plasmodium falciparum strain (W2) and for cytotoxicity to HepG2 cells. Low growth inhibition of P. falciparum as well as low cytotoxicity to HepG2 cells were observed for the essential oil. The leaves dichloromethane extract showed moderate growth inhibition of P. falciparum and low cytotoxicity to HepG2 cells. Bioguided chromatographic fractionation of this extract led to fractions with increased antiplasmodial activity from which liriodenine (IC50 6.1 ± 0.1 μg/mL, CC50 > 1000.0 μg/mL, SI > 164), an aporphine alkaloid, and an acetogenin-rich fraction containing mainly isomers of annomontacin and 4-deoxy-annomontacin (IC50 22.7 ± 1.9 µg/mL, CC50 336.1 ± 15.5 µg/mL, SI = 15) might be highlighted for their antiplasmodial activity.
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    Synthesis by click reactions and antiplasmodial activity of Lupeol 1,2,3-Triazole derivatives.
    (2017) Borgati, Tatiane Freitas; Pereira, Guilherme Rocha; Brandão, Geraldo Célio; Santos, Juliana de Oliveira; Fernandes, Dayane Aparecida Morais; Paula, Renata Cristina de; Nascimento, Maria Fernanda Alves do; Soares, Luciana Ferreira; Lopes, Júlio César Dias; Souza Filho, José Dias de; Oliveira, Alaíde Braga de
    Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity lupeol derivatives, five new 1,2,3-triazole hybrid molecules were synthetized by copper-catalyzed azide-alkyne cycloaddition. The antiplasmodial activity of the semi-synthetic compounds were evaluated by the lactate dehydrogenase assay; the lupeol propargyl ether was the only one to disclosing increased activity (half maximal inhibitory concentration-IC50-62.0 ± 1.92 μmol L-1) in relation to lupeol (IC50 117.00 μmol L-1). Therefore, this work revealed a new class of interesting lupeol derivatives that can be obtained by linking electron donors to the hydroxy group at C-3.