DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
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Item Virucidal antiviral activity of Maytenus quadrangulata extract against Mayaro virus : evidence for the presence of catechins.(2023) Nunes, Damiana Antônia de Fátima; Lopes, Gabriela Francine Martins; Nizer, Waleska Stephanie da Cruz; Aguilar, Mariana Guerra de; Santos, Felipe Rocha da Silva; Sousa, Grasiely Faria de; Ferraz, Ariane Coelho; Duarte, Lucienir Pains; Brandão, Geraldo Célio; Vieira Filho, Sidney Augusto; Magalhães, Cíntia Lopes de Brito; Ferreira, Jaqueline Maria Siqueira; Magalhães, José Carlos deEthnopharmacological relevance: Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention. Aim of the study: This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV. Materials and methods: Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50). Results: The leaves (LAE; EC50 12.0 μg/mL) and branches (TAE; EC50 101.0 μg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells.Item Anti–zika virus activity and isolation of flavonoids from ethanol extracts of Curatella americana L. leaves.(2023) Lima, Lienne D’Auria; Reis, Adriana Cotta Cardoso; Sousa, Jordano Augusto Carvalho; Valente, Gabriel Mendonça; Silva, Breno de Mello; Magalhães, Cíntia Lopes de Brito; Kohlhoff, Markus; Teixeira, Luiz Fernando de Medeiros; Brandão, Geraldo CélioThe ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian Cerrado, whose ethanolic extract showed significant in vitro anti–Zika virus activity by the MTT colorimetric method. Currently, there is no drug in clinical use specifically for the treatment of this virus; therefore, in this work, the antiviral and cytotoxic properties of the ethanolic extract, fractions, and compounds were evaluated. The ethanolic extract of the leaves showed no cytotoxicity for the human MRC-5 cell and was moderately cytotoxic for the Vero cell (CC50 161.5 ± 2.01 μg/mL). This extract inhibited the Zika virus multiplication cycle with an EC50 of 85.2 ± 1.65 μg/mL. This extract was fractionated using the liquid–liquid partition technique, and the ethyl acetate fraction showed significant activity against the Zika virus with an EC50 of 40.7 ± 2.33 μg/mL. From the ethyl acetate fraction, the flavonoids quercetin-3-O-hexosylgallate (1), quercetin-3-O-glucoside (2), and quercetin (5) were isolated, and in addition to these compounds, a mixture of quercetin-3- O-rhamnoside (3) and quercetin-3-O-arabinoside (4) was also obtained. The isolated compounds quercetin and quercetin-3-O-hexosylgallate inhibited the viral cytopathic effect at an EC50 of 18.6 ± 2.8 and 152.8 ± 2.0, respectively. Additionally, analyses by liquid chromatography coupled to a mass spectrometer allowed the identification of another 24 minor phenolic constituents present in the ethanolic extract and in the ethyl acetate fraction of this species.Item High-resolution mass spectrometry identification and characterization of flavonoids from Fridericia chica leaves extract with anti-arbovirus activity.(2022) Cruz, Ana Flávia Gomes da; Reis, Adriana Cotta Cardoso; Sousa, Jordano Augusto Carvalho; Vaz, Luana Beatriz Araújo; Silva, Breno de Mello; Magalhães, Cíntia Lopes de Brito; Kohlhoff, Markus; Oliveira, Alaíde Braga de; Brandão, Geraldo CélioPlant extracts are complex mixtures that are difficult to characterize, and mass spectrometry is one of the main techniques currently used in dereplication processes. Fridericia chica is a species with medicinal uses in Latin American countries, used in the treatment of inflammatory and infectious diseases. Extracts of this plant species are characterized by the presence of anthocyanidins. In this study, using high-resolution mass spectrometry coupled with liquid chromatography, it was possible to determine the molecular formula of thirty-nine flavonoids. Fragmentation analysis, ultraviolet spectrum and nuclear magnetic resonance data allowed the partial characterization of the structures of these compounds. The spectral dataset allowed the identification of a series of flavones in addition to the desoxyanthocyanidins common in extracts of the species. The occurrence of some of the proposed structures is uncommon in extracts of species of the Bignoniaceae family, and they are reported for the first time in the extract of this species. Quantitative analyses of total flavonoids confirmed the high content of these constituents in the species, with 4.09 ± 0.34 mg/g of dry plant material. The extract under study showed low in vitro cytotoxicity with CC50 ≥ 296.7 ± 1.4 μg/mL for Vero, LLC-MK2 and MRC-5 cell lines. In antiviral activity assays, inhibition of the cytopathic effects of Dengue, Zika and Mayaro viruses was observed, with EC50 values ranging between 30.1 and 40.9 μg/mL. The best result was observed against the Mayaro virus, with an EC50 of 30.1 μg/mL.Item Synthesis, trypanocidal and cytotoxic activities of α,β-unsaturated ketones derived from eugenol and analogues.(2022) Reis, Rúbia Castro Fernandes Melo; Reis, Adriana Cotta Cardoso; Torchelsen, Fernanda Karoline Vieira da Silva; Lana, Marta de; Sales Júnior, Policarpo Ademar; Brandão, Geraldo Célio; Braga, Saulo Fehelberg Pinto; Souza, Thiago Belarmino deThis work describes the synthesis, structural characterization, trypanocide and cytotoxic evaluation of α,β-unsaturated ketones derived from eugenol and analogues. Among the synthesized compounds, the cyclopentanonic/dihydroeugenol derivative 12 was active against amastigote forms of Trypanosoma cruzi at 5.2 nM (700 times more potent than benznidazole) and represents a potential hit for future structural optimizations to reduce its toxicity. All the compounds were also evaluated against a healthy human and four cancer cell lines and the derivative 10 was more active than doxorubicin against three cancer cells (IC50 values between 2.03–23.51 μM) and showed the higher selectivity index considering the human cells. Derivative 14 was also more potent and selective than doxorubicin against two cancer cells (IC50 values between 4.71–8.86 μM).Item Chromatographic profile of xanthones and flavonoids in the anti-dengue extracts of Fridericia samydoides (Cham.) L.G. Lohmann (Bignoniaceae).(2022) Fonseca, Juliane Morais da; Reis, Adriana Cotta Cardoso; Pereira, Guilherme Rocha; Moura, Hélia Maria Marques de; Souza Filho, José Dias de; Silva, Breno de Mello; Brandão, Geraldo CélioThe flavonoids and xanthones present in the ethanol extracts of leaves and stems of Fridericia samydoides showed that anti-dengue activities in vitro were investigated qualitatively by liquid chromatography–ultraviolet-mass spectrometry in series. Nineteen flavones and fifteen xanthones were detected and characterized on the basis of their fragmentation pattern in the positive and negative ion mode tandem mass spectrometry spectra and ultraviolet bands. Acacetin, chrysin, vitexin, isovitexin, orientin, isoorientin, mangiferin, 2’-O-trans-caffeoylmangiferin, 2’-O-trans-coumaroylmangiferin and 2’-O-trans-cinnamoylmangiferin were identified by comparison with authentic samples. The other compounds detected were tentatively assigned by analysis of the spectral data and by comparison with literature reports. In addition, it performed the fractionation of the leaves extract leading to the isolation of mangiferin, isovitexin and isoorientin. All extracts and isolated compounds inhibited the Dengue virus replication cycle with EC50 less than 25.0 μg/mL for extracts and 272.5, 85.6 and 79.3 μg/mL for mangiferin, isovitexin and isoorientin, respectively.Item Cytotoxic activity of extracts from Tecoma species and isolated lignans.(2022) Reis, Adriana Cotta Cardoso; Silva, Breno de Mello; Souza Filho, José Dias de; Pereira, Guilherme Rocha; Brandão, Geraldo CélioA phytochemical study of Tecoma genus (Bignoniaceae) was accomplished by antitumor activity of ethanolic extracts. Species of this genus are composed of small shrubs often used as ornamental plants. The Tecoma stans species is used in folk medicine for different purposes. Recent work shows in vitro anticancer activity against human breast cancer. The ethanolic extracts from leaves and trunks of Tecoma casneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were tested in vitro. The assays used were against line tumor cells by the MTT method and the most active extracts were further studied. In this way, the ethanolic extract from T. stans var. stans trunks presented the higher cytotoxicity against the tumor cell lines studied (CC50 0.02 to 0.55 μg/ml) when compared to the other extracts tested (CC50 0.08 to 200.0 μg/ml). Accordingly, this extract was selected for chromatographic fractionation from which five known lignans were isolated. Further, paulownin, paulownin acetate, sesamin, olivil and cycloolivil were identified using 13C and 1 H NMR, IR, UV and spectroscopy and spectrometric MS techniques. These isolated compounds were tested and exhibited CC50 ranging from 13.01 to100.0 μg/ml which is superior to the ethanolic extract of trunk of T. stans.Item Glucosyl-1,2,3-triazoles derived from eugenol and analogues : synthesis, anti-Candida activity, and molecular modeling studies in CYP-51.(2021) Magalhães, Lorena Severiano de; Reis, Adriana Cotta Cardoso; Nakao, Izadora Amaral; Péret, Vinícius Augusto Campos; Reis, Rúbia Castro Fernandes Melo; Silva, Naiara Chaves; Dias, Amanda Latercia Tranches; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira; Brandão, Geraldo Célio; Braga, Saulo Fehelberg Pinto; Souza, Thiago Belarmino deThis work describes the synthesis, anti-Candida, and molecular modeling stud- ies of eighteen new glucosyl-1,2,3-triazoles derived from eugenol and corre- lated phenols. The new compounds were characterized by combined Fourier Transform Infrared, 1 H and 13C nuclear magnetic resonance and spectroscopy of high-resolution mass spectrometry. The synthesized compounds did not show significant cytotoxicity against healthy fibroblast human cells (MCR-5) providing interesting selectivity indexes (SI) to active compounds. Considering the antifun- gal activity, nine compounds showed anti-Candida potential and the peracety- lated triazoles 17 and 18 were the most promising ones. Eugenol derivative 17 was active against three species of Candida at 26.1–52.1 μM. This compound was four times more potent than fluconazole against Candida krusei and less toxic (SI > 6.6) against the MCR-5 cells than fluconazole (SI > 3.3) considering this strain. Dihydroeugenol derivative 18 showed similar activity to 17 and was four times more potent and less toxic than fluconazole against C. krusei. The deacety- lated glucosides and non-glucosylated corresponding derivatives did not show considerable antifungal action, suggesting that the acetyl groups are essential for their anti-Candida activity. Molecular docking coupled with molecular dynam- ics showed that 14α-lanosterol demethylase is a feasible molecular target, since 17 and 18 could bind to this enzyme once deacetylated in vivo, thereby acting as prodrugs. Also, these studies demonstrated the importance of hydrophobic sub- stituents at the phenyl ring.Item Anti-zika activity of Ouratea semiserrata and dereplication of its constituents.(2021) Ferreira, Gabriel Monteze; Silva, Breno de Mello; Souza, Gustavo Henrique Bianco de; Oliveira, Alaíde Braga de; Brandão, Geraldo CélioZika virus is an arbovirus that has vector mosquitoes of the genus Aedes. In adult humans, the infection may be asymptomatic or present mild symptoms such as itching and low fever. However, the infection is associated with other severe problems, which encouraged investigations for an effective treatment against this virus. This work evaluated the potential anti-Zika virus effect of the ethanolic extract of Ouratea semiserrata (Mart. & Nees) Engl., Ochnaceae, a medicinal plant popularly used in Brazil for the treatment of viral infections. The extract of the stems was prepared by cold percolation using ethanol as solvent and its content dereplicated by ultra-high-performance liquid chromatography-diode array detector-tandem mass spectrometry. Phenolic com- pounds including rutin, catechin, and epicatechin were identified as the major constituents. The antiviral activity was tested in vitro against Zika virus by the MTT colorimetric method. The ethanol extract inhibited the viral replication cycle with an EC50 of 37.5 μg/ml, and at the concentration of 100 μg/ml, a 100% inhibition of the viral cytopathic effect was obtained. Rutin and epicatechin inhibited viral cytopathic effect in Vero cells with EC50 > 50.00 μg/ml.Item In vitro and in silico investigation of the photoprotective and antioxidant potential of Protium spruceanum leaves and its main flavonoids.(2022) Amparo, Tatiane Roquete; Silva, Anne Cherem Peixoto da; Seibert, Janaína Brandão; Silva, Débora dos Santos da; Santos, Viviane Martins Rebello dos; Vieira, Paula Melo de Abreu; Brandão, Geraldo Célio; Souza, Gustavo Henrique Bianco de; Santos, Bianca Aloise Maneira CorrêaFor the first time, the photoprotective potential (UV absorption and antioxidant properties) of Protium spru- ceanum leaves and its main flavonoids was investigated combining an in vitro and in silico approach. The extract was standardized in rutin content (0.8% w/w), quantified by a validated HPLC-DAD method. The extract pro- tected fibroblasts and keratinocytes against cell death in the stress oxidative H2O2-induced test, with greater effect than rutin standard. This cytoprotection is correlated to the free radical scavenging action, determined by DPPH method. The theoretical investigation on the UV absorption showed an excellent correlation of the results (R2 = 0.911) allowing valuable information about the photoprotective properties of rutin, afzelin and quercitrin, as the importance of the A, B and C rings in the UV absorption property and the hydroxyls in B ring (catechol group) leading to a better antioxidant action. Therefore, the extract from P. spruceanum leaves is a promising candidate for sunscreen development.Item Activity of alkaloids from Aspidosperma nitidum against Leishmania (Leishmania) amazonensis.(2022) Veiga, Andreza do Socorro Silva da; Silveira, Fernando Tobias; Silva, Edilene Oliveira da; Diniz Júnior, José Antônio Picanço; Araújo, Sanderson Corrêa; Campos, Marliane Batista; Marinho, Andrey Moacir do Rosário; Brandão, Geraldo Célio; Vale, Valdicley Vieira; Percário, Sandro; Dolabela, Maria FâniThis study evaluated the morphological changes caused by fractions and subfractions, obtained from barks of Aspidosperna nitidum, against L. (L.) amazonensis promastigotes. The ethanolic extract (EE) obtained through the maceration of trunk barks was subjected to an acid–base partition, resulting the neutral (FN) and the alkaloid (FA) fractions, and fractionation under refux, yielded hexane (FrHEX), dichloromethane (FrDCL), ethyl acetate (FrACoET), and methanol (FrMEOH) fractions. The FA was fractionated and three subfractions (SF5-6, SF8, and SF9) were obtained and analyzed by HPLC–DAD and 1 H NMR. The antipromastigote activity of all samples was evaluated by MTT, after that, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for the active fractions were performed. Chromatographic analyzes suggest the presence of alkaloids in EE, FN, FA, and FrDCL. The fractionation of FA led to the isolation of the indole alkaloid dihydrocorynantheol (SF8 fractions). The SF5-6, dihydrocorynantheol and SF-9 samples were active against promastigotes, while FrDCL was moderately active. The SEM analysis revealed cell rounding and changes in the fagellum of the parasites. In the TEM analysis, the treated promastigotes showed changes in fagellar pocket and kinetoplast, and presence of lipid inclusions. These results suggest that alkaloids isolated from A. nitidum are promising as leishmanicidal.