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dc.contributor.authorSiqueira, Raoni Pais
dc.contributor.authorBarros, Marcus Vinícius de Andrade
dc.contributor.authorBarbosa, Éverton de Almeida Alves
dc.contributor.authorOnofre, Thiago Souza
dc.contributor.authorGonçalves, Victor Hugo Sousa
dc.contributor.authorPereira, Higor Sette
dc.contributor.authorSilva Júnior, Abelardo
dc.contributor.authorOliveira, Leandro Licursi de
dc.contributor.authorAlmeida, Márcia Rogéria
dc.contributor.authorFietto, Juliana Lopes Rangel
dc.contributor.authorTeixeira, Róbson Ricardo
dc.contributor.authorBressan, Gustavo Costa
dc.description.abstractThe 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.en
dc.publisherEuropean Journal of Medicinal Chemistrypt-BR
dc.relation.ispartofseriesv. 134, p. 97-109, July 2017pt-BR
dc.rightsElsevier Masson
dc.subjectTrifluoromethyl arylamidespt-BR
dc.subjectSerine/arginine-rich protein kinasept-BR
dc.subjectPre-mRNA splicingpt-BR
dc.titleTrifluoromethyl arylamides with antileukemia effect and intracellular inhibitory activity over serine/arginine-rich protein kinases (SRPKs)en
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