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J Pharm Pharmacol ; 73(6): 808-815, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33730148

RESUMO

OBJECTIVES: In cancer treatment, it is important to prevent or slow down metastasis as well as preventing the proliferation of cancer cells. In this study, we aimed to find pyrazole compounds with antimigratory properties. METHODS: The 'PASSonline' programme was used to determine the possible pharmacological activities of the pyrazole compounds selected from the library, and two pyrazole derivatives were identified as a transcription factor STAT inhibitor with a high probability. There are studies known that JAK/STAT pathway is related to cancer cell migration, thus the possible antimigratory effects of these two synthesized pyrazole compounds were examined in A549 cancer cells. KEY FINDINGS: Our data demonstrated that compound-2 at different concentrations significantly inhibited cell migration in A549 cells. Then, the effects of these compounds on STAT activation were evaluated. We reported that 10 µM compound-2 induced a significant phosphorylation of STAT1 suggesting that STAT1 activation may be responsible for the antimigratory effect of compound-2. CONCLUSIONS: Taken together, the compound-2 is a promising compound with the antimigratory activity for cancer treatment, and further studies are needed to synthesize more active derivatives by evaluating the structure-activity relationship of leading compound-2.


Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Pirazóis/farmacologia , Células A549 , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Relação Dose-Resposta a Droga , Humanos , Fosforilação/efeitos dos fármacos , Pirazóis/administração & dosagem , Pirazóis/química , Fator de Transcrição STAT1/metabolismo , Relação Estrutura-Atividade
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