Navegando por Autor "Pereira, Guilherme Rocha"

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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.
Anti-Zika virus activity and chemical characterization by ultra-high performance liquid chromatography (UPLC-DAD-UV-MS) of ethanol extracts in Tecoma species.
(2020) Reis, Adriana Cotta Cardoso; Silva, Breno de Mello; Moura, Hélia Maria Marques de; Pereira, Guilherme Rocha; Brandão, Geraldo Célio
Background: Plant species from the genus Tecoma are found in tropical and subtropical regions around the world. Some of them are grown as ornamental plants and others can be used as medicinal plants. In the present study, ethanolic extracts from trunks and leaves of Tecoma species were tested in vitro using assays against the Zika virus. Methods: There was a total of 8 extracts obtained from different anatomical parts of three Tecoma species. The Tecoma castaneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were prepared by percolation with ethanol. The antiviral activity was assayed in vitro against the Zika virus by the MTT colorimetric method (n = 3). The UPLC-DAD-MS analysis of ethanolic extracts was performed from all the studied species. The biofractionation of T. stans var. stans trunk extract using different separation techniques led to the isolation of crenatoside compound. Results: Ethanolic extract from Tecoma species leaves were more active against the Zika virus (EC50 149.90 to 61.25 μg/mL) when compared to the trunk extracts tested (EC50 131.0 to 66.79 μg/mL and two were not active). The ethyl acetate and aqueous fractions obtained from T. stans var. stans trunk were active against the Zika virus with EC50 values of 149.90 and 78.98 μg/mL, respectively. Crenatoside is a phenylethanoid glycoside isolated from the ethyl acetate of T. stans var. stans trunk extract. This compound was tested and exhibited EC50 34.78 μM (21.64 μg/mL), thus demonstrating a better result than the original ethanolic extracts as well as others extracts of Tecoma species, and it was more active than the positive control, ribavirin (386.84 μM). Furthermore, its selectivity index was at least 2.5 times higher than the tested ethanolic extracts and 11.1 times more potent than ribavirin. Conclusion: The Tecoma species demonstrated interesting in vitro activity against the Zika virus. The crenatoside, phenylethanoid glycoside that was for the first time isolated from Tecoma stans var. stans, exhibited a potent and relevant anti-Zika virus activity, being more active than ribavirin (positive control). The data show that crenatoside, was a promising compound with in vitro antiviral activity against the Zika virus.
A chloroquinoline derivate presents effective in vitro and in vivo antileishmanial activity against Leishmania species that cause tegumentary and visceral leishmaniasis.
(2019) Sousa, Jéssica Karine Távora de; Antinarelli, Luciana Maria Ribeiro; Mendonça, Débora Vasconcelos Costa; Lage, Daniela Pagliara; Tavares, Grasiele de Sousa Vieira; Dias, Daniel Silva; Ribeiro, Patrícia Aparecida Fernandes; Ribeiro, Fernanda Ludolf; Coelho, Vinicio Tadeu da Silva; Silva, João Augusto Oliveira da; Melo, Luísa Helena Perin de; Oliveira, Bianka A.; Alvarenga, Denis Fernando; Chávez Fumagalli, Miguel Angel; Brandão, Geraldo Célio; Vandack, Nobre; Pereira, Guilherme Rocha; Coimbra, Elaine Soares; Coelho, Eduardo Antônio Ferraz
The identification of new therapeutics to treat leishmaniasis is desirable, since available drugs are toxic and present high cost and/or poor availability. Therefore, the discovery of safer, more effective and selective pharmaceutical options is of utmost importance. Efforts towards the development of new candidates based on molecule analogs with known biological functions have been an interesting and cost-effective strategy. In this context, quinoline derivatives have proven to be effective biological activities against distinct diseases. In the present study, a new chloroquinoline derivate, AM1009, was in vitro tested against two Leishmania species that cause leishmaniasis. The present study analyzed the necessary inhibitory concentration to preclude 50% of the Leishmania promastigotes and axenic amastigotes (EC50 value), as well as the inhibitory concentrations to preclude 50% of the murine macrophages and human red blood cells (CC50 and RBC50 values, respectively). In addition, the treatment of infected macrophages and the inhibition of infection using pre-treated parasites were also investigated, as was the mechanism of action of the molecule in L. amazonensis. To investigate the in vivo therapeutic effect, BALB/c mice were infected with L. amazonensis and later treated with AM1009. Parasitological and immunological parameters were also evaluated. Clioquinol, a known antileishmanial quinoline derivate, and amphotericin B (AmpB), were used as molecule and drug controls, respectively. Results in both in vitro and in vivo experiments showed a better and more selective action of AM1009 to kill the in vitro parasites, as well as in treating infected mice, when compared to results obtained using clioquinol or AmpB. AM1009-treated animals presented significantly lower average lesion diameter and parasite burden in the infected tissue and organs evaluated in this study, as well as a more polarized antileishmanial Th1 immune response and low renal and hepatic toxicity. This result suggests that AM1009 should be considered a possible therapeutic target to be evaluated in future studies for treatment against leishmaniasis.
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 Célio
The 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.
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 Célio
A 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.
Novel lignan-based compounds via click chemistry : paulownin isolation, structural modifications and cytotoxic activity evaluations.
(2020) Pereira, Guilherme Rocha; Ferreira, Andreza Cristina Gomes; Costa, Flávia; Munhoz, Victor Hugo; Alvarenga, Denis Fernando; Silva, Breno de Mello; Reis, Adriana Cotta Cardoso; Brandão, Geraldo Célio
Paulownin, a natural compound obtained from the tree Tecoma stans var. stans, was chemically modified by alkylation of its hydroxyl position. Thirteen novel lignans derivatives synthesized via a copper-catalyzed cycloaddition (CuAAC), known as click reaction, using different organic azides and lignan terminal alkyne. Characterization by mass spectrometry, NMR (1 H and 13C) and infrared spectroscopy. These novel molecules were submitted to biological tests, using the MTT colorimetric technique aiming at the verification of their antitumor properties with six different cells lines. Biological evaluation was satisfactory and one of compounds showed selectivity index ten times higher than podophyllotoxin.
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.