Use este identificador para citar ou linkar para este item: https://locus.ufv.br//handle/123456789/19944
Tipo: Artigo
Título: Trifluoromethyl arylamides with antileukemia effect and intracellular inhibitory activity over serine/arginine-rich protein kinases (SRPKs)
Autor(es): 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 Costa
Abstract: The 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.
Palavras-chave: Trifluoromethyl arylamides
SRPK
SRPIN340
Serine/arginine-rich protein kinase
Leukemia
Pre-mRNA splicing
Editor: European Journal of Medicinal Chemistry
Tipo de Acesso: Elsevier Masson SAS.
URI: https://doi.org/10.1016/j.ejmech.2017.03.078
http://www.locus.ufv.br/handle/123456789/19944
Data do documento: 31-Mar-2017
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