Navegando por Autor "Gonçalves, Victor Hugo Sousa"
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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 Prospecção tecnológica e desenvolvimento de estratégias de diagnóstico de leptospirose(Universidade Federal de Viçosa, 2022-07-15) Gonçalves, Victor Hugo Sousa; Bressan, Gustavo Costa; http://lattes.cnpq.br/0200670915699187A leptospirose é uma doença infecciosa febril causada por variedades patogênicas do gênero Leptospira, e é considerada uma das zoonoses de maior projeção mundial. Os roedores são os principais reservatórios dessas bactérias, mas outros animais silvestres e domésticos, como equinos, bovinos e cães, também participam da sua transmissão, que se dá principalmente através do contato com a urina de indivíduos infectados. Apesar do crescente interesse na área, ainda ha uma falta de alternativas acessíveis e eficientes para o diagnóstico de leptospirose em cães. Assim, neste trabalho propomos a utilização de duas proteinas quiméricas como antígenos para o diagnóstico sorológico de leptospirose canina. As proteinas recombinantes foram produzidas em E. coli, e recuperadas purificadas com rendimento de 4,467 e 77,957 mg/L. Foi empregado a técnica de ELISA indireto, utilizando ambas as quimeras como antígeno, para detectar anticorpos dos tipos IgG e IgM em amostras de soro. Resultados de MAT das amostras foram utilizados como referência para avaliação da eficiência do diagnóstico por ELISA. Foram avaliadas diferentes condições para o diagnóstico, e a acurácia geral dos ensaios variou de 57 à 80 %, sendo que a capacidade de predição de valores positivos foi de aproximadamente 85 % para IgG e 75 % para IgM. Demonstramos assim que as quimeras construídas apresentam potencial para auxiliar no diagnóstico de leptospirose canina. Além disso, foi construído um patent landscape com objetivo de descrever o cenário de desenvolvimento de soluções biotecnológicas para o campo de doenças infecciosas caninas. Esses dados demonstraram a relevante participação das instituições de ensino públicas no desenvolvimento de produtos de biotecnologia, e reforçaram a importância das parcerias público-privadas no avanço científico. Palavras-chave: Leptospira. Leptospirose em animais. Diagnóstico. Ensaio de imunoabsorção enzimática.Item Síntese e avaliação da atividade citotóxica de derivados do eugenol contendo núcleos 1,2,3-triazólicos(Química Nova, 2018-05) Gazolla, Poliana Aparecida Rodrigues; Teixeira, Róbson Ricardo; Silva, Adalberto Manoel da; Vaz, Boniek Gontijo; Vasconcelos, Géssica Adriana; Siqueira, Raoni Pais; Gonçalves, Victor Hugo Sousa; Pereira, Higor Sette; Bressan, Gustavo CostaEugenol is an aromatic compound found in several plant species. It presents important biological activities including cytotoxicity. In this paper, it is described the synthesis and the evaluation of the cytotoxic activity of eugenol derivatives bearing 1,2,3-triazole functionalities. Eugenol, extracted via hydrodistillation from dried flower buds of Eugenia caryophyllata (=Syzygium aromaticum), was submitted to alkylation reactions to afford two terminal alkynes in good yields. The key reaction involved in the preparation of eugenol derivatives corresponded to the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC), between alkynylated eugenol derivatives and different benzyl azides. The evaluation of the cytotoxicity of twenty seven synthesized derivatives against HL60 leukemia cell line revealed that at 100 µmol L-1, five of them, namely 4-((4-allyl-2-methoxyphenoxy)methyl)-1-(3-bromobenzyl)-1H-1,2,3-triazole (6n), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-benzyl-1H-1,2,3-triazole (7a), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-chlorobenzyl)-1H-1,2,3-triazole (7c), 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-iodobenzyl)-1H-1,2,3-triazole (7e) and 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(3-bromobenzyl)-1H-1,2,3-triazole (7m), were capable of significantly decreasing cell viability. These most active triazolic derivatives were also evaluated against B16F10 melanoma and Nalm6 leukemia cell lines. While only compound 7a was active against the former, compounds 6n, 7a, and 7m displayed activity against the latter. Derivative 7a was active against all cell lines. It is believed that eugenol derivatives bearing triazole functionalities may represent a scaffold to be explored toward the development of new agents against cancer.Item Trifluoromethyl arylamides with antileukemia effect and intracellular inhibitory activity over serine/arginine-rich protein kinases (SRPKs)(European Journal of Medicinal Chemistry, 2017-03-31) Siqueira, Raoni Pais; Barros, Marcus Vinícius de Andrade; Barbosa, Éverton de Almeida Alves; Onofre, Thiago Souza; Gonçalves, Victor Hugo Sousa; Pereira, Higor Sette; Silva Júnior, Abelardo; Oliveira, Leandro Licursi de; Almeida, Márcia Rogéria; Fietto, Juliana Lopes Rangel; Teixeira, Róbson Ricardo; Bressan, Gustavo CostaThe serine/arginine-rich protein kinases (SRPKs) have frequently been found with altered activity in a number of cancers, suggesting they could serve as potential therapeutic targets in oncology. Here we describe the synthesis of a series of twenty-two trifluoromethyl arylamides based on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and the evaluation of their antileukemia effects. Some derivatives presented superior cytotoxic effects against myeloid and lymphoid leukemia cell lines compared to SRPIN340. In particular, compounds 24, 30, and 36 presented IC50 values ranging between 6.0 and 35.7 μM. In addition, these three compounds were able to trigger apoptosis and autophagy, and to exhibit synergistic effects with the chemotherapeutic agent vincristine. Furthermore, compound 30 was more efficient than SRPIN340 in impairing the intracellular phosphorylation status of SR proteins as well as the expression of MAP2K1, MAP2K2, VEGF, and RON oncogenic isoforms. Therefore, novel compounds with increased intracellular effects against SRPK activity were obtained, contributing to medicinal chemistry efforts towards the development of new anticancer agents.