Navegando por Autor "Evangelista, Fernanda Cristina Gontijo"
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Item Are the polymorphisms in ACE and ESR1 genes associated with preeclampsia occurrence?(2019) Lopes, Ana Cristina dos Santos; Perucci, Luiza Oliveira; Evangelista, Fernanda Cristina Gontijo; Godoi, Lara Carvalho; Sabino, Adriano de Paula; Silva, André Talvani Pedrosa da; Dusse, Luci Maria Sant'Ana; Alpoim, Patrícia NessrallaItem Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.(2019) Lopes, Ana Cristina dos Santos; Perucci, Luiza Oliveira; Evangelista, Fernanda Cristina Gontijo; Godoi, Lara Carvalho; Sabino, Adriano de Paula; Gomes, Karina Braga; Silva, André Talvani Pedrosa da; Dusse, Luci Maria Sant'Ana; Alpoim, Patrícia NessrallaBackground: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. Material and Methods: This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. Results: No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. Conclusion: This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.Item Imines and lactones derived from friedelanes and their cytotoxic activity.(2018) Aguilar, Mariana Guerra de; Sousa, Grasiely Faria de; Evangelista, Fernanda Cristina Gontijo; Sabino, Adriano de Paula; Vieira Filho, Sidney Augusto; Duarte, Lucienir PainsFriedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovar- ian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.Item Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs.(2018) Andrade, Silmara Nunes; Evangelista, Fernanda Cristina Gontijo; Seckler, Diego Eduardo Lima; Marques, Deisielly Ribeiro; Freitas, Tulio Resende; Nunes, Renata Rachide; Oliveira, Júlia Teixeira de; Ribeiro, Rosy Iara Maciel de Azambuja; Santos, Helio Batista dos; Thomé, Ralph Gruppi; Taranto, Alex Gutterres; Santos, Fabio Vieira dos; Viana, Gustavo Henrique Ribeiro; Freitas, Rossimiriam Pereira de; Humberto, Jorge Luiz; Sabino, Adriano de PaulaBreast and ovarian cancer are the most common cancers in women. Available cancer treatments, in general, have limited efficacy and frequent, undesirable side effects. Recently, scientists have focused on searching for new epigenetic modulators such as inhibitors of DNA methyltransferases and histone deacetylases (HDACs), with novel properties and selectivity. We report the synthesis of seven new analogs of Santacruzamate A. Molecular modeling showed that compounds 3–9 presented the best binding energies (kcal/mol) against HDAC4 compared to that of crystallographic ligand. The compounds were evaluated against MCF-7 and MDA-MB-231 (breast cancer), TOV-21G (ovarian adenocarcinoma), and WI-26VA4 (non-tumor lung fibroblasts) cells. Compound 5, the most potent and selective of the series, exhibited remarkably enhanced anticancer potency, with IC50 values for the tumor cells of 24.3–44.93 μM, compared with that of etoposide (12–18.57 μM) and doxorubicin (2.1–4.37 μM). Further investigation showed that compound 5 could promote DNA damage, increase the activity of caspases-3 and -9, and upregulate mRNA levels of p21, TP53, and BAK, suggesting apoptotic cell death of the tumor cells via the intrinsic pathway. This study demonstrated that synthetic analogs of santacruzamate A with zinc-linked groups are effective for improving both HDAC inhibition and antitumor activity.