DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
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 Effects of experimental conditions on solubility measurements for BCS classification in order to improve the biowaiver guidelines.(2021) Monteiro, Patrícia Fernanda; Barcellos, Neila Marcia Silva; Caldeira, Tamires Guedes; Reis, Adriana Cotta Cardoso; Ribeiro, Amanda Santos; Souza, Jacqueline deAmong the methods described for determining the solubility, shake-flask is suitable to evaluate the equilibrium solubility according to the BCS. Nevertheless, experimental conditions related to the shake-flask method are not well described. Evaluating the effects of experimental conditions on solubility measurements by shake-flask method is important and contributes in biowaiver decision. For this work, propranolol hydrochloride and nimesulide were used as model compound of high and low solubility, respectively. Equilibrium solubility was evaluated at 37 oC, 100 rpm during 48 hours in buffer media. Effects of the rotation speed, temperature, substance in excess and aliquot withdrawn were evaluated. Small variations of temperature caused significant differences in the solubility and then this parameter must be controlled. Excess of raw material influenced the results of the nimesulide, then, little excess is recommended. Rotation speed did not cause differences in the equilibrium solubilities, but at 150 rpm the equilibrium was reached faster. Aliquot did not present significant differences, but excessive withdrawn should be avoided. Therefore, the evaluation of equilibrium solubility using shake-flask method must be performed in physiological pH conditions, 37 ± 1 oC, substance in excess 10% above saturation, 50, 100 or 150 rpm and aliquot withdrawn not more than 10% of the media volume.Item Synthesis and structural characterization of new benzylidene glycosides, cytotoxicity against cancer cell lines and molecular modeling studies.(2021) Péret, Vinícius Augusto Campos; Reis, Adriana Cotta Cardoso; Silva, Naiara Chaves; Dias, Amanda Latercia Tranches; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira; Braga, Saulo Fehelberg Pinto; Brandão, Geraldo Célio; Souza, Thiago Belarmino deThis work describes the synthesis, structural characterization (by combined Fourier Transform Infrared - FTIR, 1H and 13C Nuclear Magnetic Resonance - NMR spectroscopy and High Resolution Mass Spectrometry - HRMS) and biological evaluation of a new series of glycosides designed from a benzylidene glucoside derived from eugenol (23) active against Candida glabrata. The mass accuracy between the calculated and found values observed in HRMS analyses were lower than 5 ppm, which are acceptable for proposing a molecular formula using this technique. We decided to keep the benzylidene group of 23, while changing either the saccharide unit (glucose or galactose) or the natural aglycone (eugenol, isoeugenol, dihydroeugenol or guaiacol) to check their influence in antifungal activity. Since the chemical modifications performed did not contribute to enhance the antifungal activity, the synthesized compounds (23– 30) were further screened against four cancer cell lines (HeLa: cervix carcinoma; MDA-MB-231: breast carcinoma; T-24: urinary bladder carcinoma; and TOV-21G: ovarian carcinoma). The glucoside 27 showed promising activities (IC50 10.08–59.91 μM) against all the assayed cancer cell lines and higher values of selectivity index than doxorubicin, the control drug. The galactoside 28 demonstrated interesting results against HeLa, MDA-MB-231 and T-24 cells. This compound was active at 17.41 μM with a selectivity index greater than 13.7 against the HeLa cells, while doxorubicin was active at 10.01 μM with a selectivity index close to 1.5 considering this cell line. Further, we performed docking studies of these compounds with type II topoisomerase-DNA complex (TOP2) in order to try to explain their mechanism of action.Item Synthesis, chemical characterization and antimicrobial activity of new acylhydrazones derived from carbohydrates.(2019) Guilherme, Fernanda Dias; Simonetti, Julia Évelin; Folquitto, Laís Regina dos Santos; Reis, Adriana Cotta Cardoso; Oliver, Josidel Conceição; Dias, Amanda Latercia Tranches; Dias, Danielle Ferreira; Carvalho, Diogo Teixeira; Brandão, Geraldo Célio; Souza, Thiago Belarmino deA new series of glycosylated acylhydrazones was synthesized and all the chemical structures were confirmed by High Resolution Mass Spectrometry (HRMS), 1 H and 13C Nuclear Magnetic Resonance (1 HNMR; 13C-NMR) and Fourier Transform Infrared (FTIR) spectroscopy methods. The mass accuracy between the calculated and found values observed in HRMS analyses were near or lower than 5 ppm, which are acceptable for proposing a molecular formula using this technique. All of the synthesized compounds were screened for their antibacterial, antifungal and antiviral activities. Five compounds (12, 13, 14, 16 and 19) exerted a modest antifungal activity against the strains evaluated. Derivative 14 showed fungicidal activity against Candida glabrata at 173.8 mM and saccharide unit contributed to the increase of the antifungal potential against this strain. New chemical manipulation of derivative 14 can make it possible to obtain new potentially antimicrobial agents.