Browsing by Author "Dias, Danielle Ferreira"

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    Anti-inflammatory, antimicrobial and acetylcholinesterase inhibitory activities of friedelanes from Maytenus robusta branches and isolation of further triterpenoids.
    (2017) Sousa, Grasiely Faria de; Aguilar, Mariana Guerra de; Dias, Danielle Ferreira; Takahashi, Jacqueline Aparecida; Moreira, Maria Eliza de Castro; Vieira Filho, Sidney Augusto; Silva, Grácia Divina de Fátima; Rodrigues, Salomão Bento Vasconcelos; Messias, Maria Cristina Teixeira Braga; Duarte, Lucienir Pains
    The new pentacyclic triterpenoids friedel-1-en-3,16-dione (1), 1α,29-dihydroxyfriedelan-3-one (2) and 16β,28,29-trihydroxyfriedelan-3-one (3) were isolated from Maytenus robusta branches in addition to the known, but new for this species, triterpenoid 12α,29-dihydroxyfriedelan-3-one (4). The structures and stereochemistry of the novel triterpenoids were established by IR, 1D/2D NMR and HR-APCIMS spectral data. In addition, the biological activity of compound 2 and the previously isolated friedelanes 5–8 (friedelan-3,16-dione, 29-hydroxyfriedelan- 3-one, 29-hydroxyfriedelan-3,16-dione and 16β,29-dihydroxyfriedelan-3-one) was investigated. Compounds 2 and 8 were tested for their acetylcholinesterase properties and antimicrobial activity against the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes, Citrobacter freundii, and the fungus Candida albicans. Compound 2 was the most active compound for both assays, with values of 32.3% acetylcholinesterase inhibition, 42% activity against the fungus Candida albicans and 34% against the bacterium Pseudomonas aeruginosa. Compounds 5–8 were assayed for their antiedematogenic activity using the carrageenan- induced paw edema assay. At maximum inflammation after three hours, compounds 6 and 8 showed 42% and 57% activity, respectively. After four hours, compounds 5 and 7 showed activity of 71% and 75% compared to 79% of the control indomethacin.
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    Benzophenone derivatives showed dual anti-inflammatory and antiproliferative activities by inhibiting cox enzymes and promote cyclin e downregulation.
    (2022) Folquitto, Laís Regina dos Santos; Souza, Thiago Belarmino de; Januário, Jaqueline Pereira; Nascimento, Isadora M.; Brandão, Brenda Tavares de Vasconcelos; Moreira, Maria E. C.; Horvath, Renato de Oliveira; Santos, Marcelo Henrique dos; Coelho, Luiz Felipe Leomil; Veloso, Marcia Paranho; Soares, Marisi Gomes; Carvalho, Diogo Teixeira; Ionta, Marisa; Paula, Daniela Aparecida Chagas de; Dias, Danielle Ferreira
    Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo anti- inflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7)showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA-MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.
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    Design and synthesis of new benzophenone derivatives with in vivo anti-inflammatory activity through dual inhibition of edema and neutrophil recruitment.
    (2018) Januário, Jaqueline Pereira; Souza, Thiago Belarmino de; Lavorato, Stefânia Neiva; Maiolini, Tatiane Cristina Silva; Domingos, Olívia da Silva; Zanin, João Luiz Baldim; Folquitto, Laís Regina dos Santos; Soares, Marisi Gomes; Paula, Daniela Aparecida Chagas de; Dias, Danielle Ferreira; Santos, Marcelo Henrique dos
    A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C40 -OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action
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    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 Latércia Tranches; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira; Brandão, Geraldo Célio; Braga, Saulo Fehelberg Pinto; Souza, Thiago Belarmino de
    This 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.
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    Phenylpropanoid-based sulfonamide promotes cyclin D1 and cyclin E downregulation and induces cell cycle arrest at G1/S transition in estrogen positive MCF-7 cell line.
    (2019) Barbosa, Helloana Azevedo; Silva, Guilherme Álvaro Ferreira da; Silva, Carolina Faria; Souza, Thiago Belarmino de; Dias, Danielle Ferreira; Paula, Ana Cláudia Chagas de; Ionta, Marisa; Carvalho, Diogo Teixeira
    Cancer is one of the most critical problems of public health in the world and one of the main challenges for medicine. Different biological effects have been reported for sulfonamide-based compounds including antibacterial, antifungal, and antitumor activities. Herein, a series of phenylpropanoid-based sulfonamides (4a, 4a′, 4b, 4b′, 5a, 5a′, 5b and 5b′) were synthesized and their cytotoxic activity was evaluated against four cell lines derived from human tumours (A549 – lung, MCF-7 – breast, Hep G2 - hepatocellular carcinoma, and HT-144-melanoma). Cell viability was significantly reduced in the MCF-7 cell line when compounds 4b, 4b′ and 5a were used; IC50 values were lower than those found for their precursors (eugenol and dihydroeugenol) and sulfanilamide. We observed that 4b induced cell cycle arrest at G1/S transition. This is probably due to its ability to reduce cyclin D1 and cyclin E expression. Moreover, 4b also induced apoptosis in MCF-7 cells as demonstrated by an increase in the cell population positive for annexin V in treated cultures in comparison to the control group. Taken together, the data showed that 4b is a promising antitumor agent and it should be considered for further in vivo studies.
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    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 de
    This 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.
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    Synthesis of eugenol-derived glucosides and evaluation of their ability in inhibiting the angiotensin converting enzyme.
    (2020) Alvarenga, Dalila Junqueira; Matias, Laira Maria Faria; Cordeiro, Cleydson Finotti; Souza, Thiago Belarmino de; Lavorato, Stefânia Neiva; Pereira, Marília Gabriella Alves Goulart; Dias, Danielle Ferreira; Carvalho, Diogo Teixeira
    We report here a series of glucosides which are active as inhibi tors of the angiotensin converting enzyme (ACE). They are struc turally related to the natural compound eugenol and exhibited significant inhibition values. Their syntheses were expeditious and we could obtain informative docking plots of them complexed to this enzyme. A glucoside derived from eugenol, carrying a carbox ylic group in the aglycone, was the most active of them (with an IC50 of 0.4 mM) and showed good binding energies in docking studies with ACE. Moreover, computational prediction of toxicity risks, physicochemical properties and drug score show that the glucoside derivative of eugenol is a suitable compound for opti misation studies aimed at finding new drug candidates.
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    Synthesis, activity, and docking studies of eugenol-based glucosides as new agents against Candida sp.
    (2018) Hipolito, Taciane Maira Magalhães; Bastos, Guilherme Tadeu Lemos; Barbosa, Thulio Wliandon Lemos; Souza, Thiago Belarmino de; Coelho, Luiz Felipe Leomil; Dias, Amanda Latercia Tranches; Rodríguez, Ihosvany Camps; Santos, Marcelo Henrique dos; Dias, Danielle Ferreira; Franco, Lucas Lopardi; Carvalho, Diogo Teixeira
    Seventeen new synthetic derivatives of eugenol (6, 8–15 and 8′‐15′) were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti‐Candida activity of these compounds was investigated by in vitro assay, and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4‐nitrobenzamide, showed the best potency (MIC50 range 11.0–151.84 μm), the wider spectrum of action, and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). To investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4‐nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.
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    Synthesis, activity, and molecular modeling studies of 1,2,3‐ triazole derivatives from natural phenylpropanoids as new trypanocidal agents.
    (2019) Souza, Thiago Belarmino de; Caldas, Ivo Santana; Paula, Favero Reisdorfer; Rodrigues, Camila Coelho; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira
    The search for compounds with new structural scaffolds is an important tool to the discovery of new drugs against Chagas disease. We report herein the synthesis of 1,2,3‐triazoles obtained from eugenol and di‐hydroeugenol and their in vitro and in vivo trypanocidal activity. These derivatives were obtained by a three‐step objective route and were suitably characterized by 1H and 13C nuclear magnetic resonance spectroscopy and high‐resolution mass spectrometry. Two compounds (9 and 10 ) showed activity against epimastigote forms of Trypanosoma cruzi (Y strain) in the range 42.8–88.4 μM and were weakly toxic to cardiomyoblast cells (H9c2 cells). The triazole 10 was the most active derivative and could reduce more than 50% of parasitemia after a 100‐mg/kg oral treatment of mice infected with T. cruzi . Molecular docking studies suggested this compound could act as a trypanocidal agent by inhibiting cruzain, an essential enzyme for T. cruzi metabolism, usually inhibited by triazole compounds.
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    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 de
    A 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.