DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
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 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, 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 TeixeiraSeventeen 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.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.