RESUMEN
A series of coumarin derivatives and isosteres were synthesized from the reaction of triflic intermediates with phenylboronic acids, terminal alkynes, and organozinc compounds through palladium-catalyzed cross-coupling reactions. The in vitro cytotoxic effect of the compounds was evaluated against two non-small cell lung carcinoma (NSCLC) cell lines (A-549 and H2170) and a normal cell line (NIH-3T3) using cisplatin as a reference drug. Additionally, the effects of the most promising coumarin derivative (9f) in reversing the epithelial-to-mesenchymal transition (EMT) in IL-1ß-stimulated A549 cells and in inhibiting the EMT-associated migratory ability in A549 cells were also evaluated. 9f had the greatest cytotoxic effect (CC50 = 7.1 ± 0.8 and 3.3 ± 0.5 µM, respectively against A549 and H2170 cells) and CC50 value of 25.8 µM for NIH-3T3 cells. 9f inhibited the IL-1ß-induced EMT in epithelial cells by inhibiting the F-actin reorganization, attenuating changes in the actin cytoskeleton reorganization, and downregulating vimentin in A549 cells stimulated by IL-1ß. Treatment of A549 cells with 9f at 7 µM for 24 h significantly reduced the migration of IL-1ß-stimulated cells, which is a phenomenon confirmed by qualitative assessment of the wound closure. Taken together, our findings suggest that coumarin derivatives, especially compound 9f, may become a promising candidate for lung cancer therapy, especially in lung cancer promoted by NSCLC cell lines.
RESUMEN
RESUMO As Instituições de saúde de ensino superior têm buscado efetuar mudanças em seus projetos político-pedagógicos, replanejando, assim, seus currículos. Esta pesquisa teve por objetivo avaliar o processo de ensino-aprendizagem no estágio supervisionado, quando realizado com a integração de estudantes de diversos cursos na área da saúde, utilizando como abordagem um estudo de caso etnográfico, por meio de observação participante, questionário semiestruturado e grupo focal. Mediante a triangulação dos dados, pôde-se perceber a importância da interdisciplinaridade, do trabalho em equipe, da contribuição para a formação profissional e do papel do docente como facilitador do processo de ensino-aprendizagem, estimulando o senso crítico e a tomada de decisão. A proposta do Estágio Integrado permite um novo olhar no processo de ensino-aprendizagem, aliada à diversificação do cenário de prática, principalmente quando se fala em ensino na saúde. O Estágio Integrado pode ser entendido como uma estratégia pedagógica para tentar superar a fragmentação do conhecimento e ser utilizado como um referencial por outras Instituições de ensino na saúde que buscam formar profissionais de saúde com perfil humanista, capazes de atuar na integralidade da atenção à saúde e em equipe.
ABSTRACT Higher education health institutions have sought to make changes to their political-pedagogical projects, thus redesigning their curricula. This study aimed to evaluate the teaching-learning process in supervised internships that integrate students from diverse health care courses, using the approach of an ethnographic case study through participant observation, semi-structured questionnaire and focus groups. Triangulated data indicates the importance of interdisciplinary structure, teamwork, the teacher’s role and contribution as facilitator of the training process, encouraging critical thinking and decision making. The proposed Integrated Internship allows a new vision of the teaching-learning process, coupled with diversified practical situations, particularly as regards education in health. It can be understood as a pedagogical strategy aimed at overcoming knowledge fragmentation and can be used as a benchmark by other educational institutions in health, seeking to train health professionals with a humanistic profile, ready to work in comprehensive health care and as part of a team.