Navegando por Autor "Moreira, Gabriela Alves"
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Item Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma(Toxicology and Applied Pharmacology, 2018-10-01) Moreira, Gabriela Alves; Lima, Graziela Domingues de Almeida; Siqueira, Raoni Pais; Barros, Marcus Vinícius de Andrade; Adjanohoun, Abraham Landry Mahuvi; Santos, Viviane Corrêa; Barbosa, Éverton de Almeida Alves; Loterio, Robson Kriiger; Paiva, Janine Cerqueira de; Gonçalves, Victor Hugo Sousa; Viol, Lívia Cristina de Souza; Marques-da-Silva, Eduardo de Almeida; Silva Júnior, Abelardo; Almeida, Márcia Rogéria; Fietto, Juliana Lopes Rangel; Machado-Neves, Mariana; Ferreira, Rafaela Salgado; et al.The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers.Item Splicing regulators and their roles in cancer biology and therapy(BioMed Research International, 2015-04-01) Silva, Maria Roméria da; Moreira, Gabriela Alves; Silva, Ronni Anderson Gonçalves da; Barbosa, Éverton de Almeida Alves; Siqueira, Raoni Pais; Teixera, Róbson Ricardo; Almeida, Márcia Rogéria; Silva Júnior, Abelardo; Fietto, Juliana Lopes Rangel; Bressan, Gustavo CostaAlternative splicing allows cells to expand the encoding potential of their genomes. In this elegant mechanism, a single gene can yield protein isoforms with even antagonistic functions depending on the cellular physiological context. Alterations in splicing regulatory factors activity in cancer cells, however, can generate an abnormal protein expression pattern that promotes growth, survival, and other processes, which are relevant to tumor biology. In this review, we discuss dysregulated alternative splicing events and regulatory factors that impact pathways related to cancer. The SR proteins and their regulatory kinases SRPKs and CLKs have been frequently found altered in tumors and are examined in more detail. Finally, perspectives that support splicing machinery as target for the development of novel anticancer therapies are discussed.Item Synthesis and antimetastatic activity evaluation of cinnamic acid derivatives containing 1,2,3-triazolic portions(Toxicology in Vitro, 2018-12) Lima, Graziela Domingues de Almeida; Rodrigues, Michelle Peixoto; Moreira, Gabriela Alves; Mendes, Tiago Antônio de Oliveira; Siqueira, Raoni Pais; Silva, Adalberto Manoel da; Vaz, Boniek Gontijo; Fietto, Juliana Lopes Rangel; Bressan, Gustavo Costa; Teixeira, Róbson Ricardo; Machado-Neves, MarianaIt is herein described the preparation and evaluation of antimetastatic activity of twenty-six cinnamic acid derivatives containing 1,2,3-triazolic portions. The compounds were prepared using as the key step the Copper(I)-catalyzed azide (A)-alkyne (A) cycloaddition (C) (CuAAC reaction), also known as click reaction, between alkynylated cinnamic acid derivatives and different benzyl azides. The reactions were carried in CH2Cl2/H2O (1:1 v/v) at room temperature, and the triazole derivatives were obtained in yields ranging from 73%99%. Reaction times varied from 5 to 40 min. The identity of the synthesized compounds was confirmed by IR and NMR (1H and 13C) spectroscopic techniques. They were then submitted to in vitro bioassays to investigate how they act over metastatic behavior of murine melanoma. The most potent compound, namely 3-(1-benzyl-1H-1,2,3-triazol-4-yl)propyl cinnamate (9a), showed significant antimetastatic and antiproliferative activities against B16-F10 cells. In addition, gelatin zymography and molecular docking analyses pointed to the fact that this compound has potential to interact with matrix metalloproteinase 9 (MMP-9) and MMP-2, which are directly involved in melanoma progression. Therefore, these findings suggest that cinnamic acid derivatives containing 1,2,3-triazolic portions may have potential for development of novel candidates for controlling malignant metastatic melanoma.