Antimigratory effect of pyrazole derivatives through the induction of STAT1 phosphorylation in A549 cancer cells

Author:

Şimay Demir Yaprak Dilber1ORCID,Özdemir Aysun1,Özdemir Reyhan Gönbe1,Cevher Setenay Cemre1ORCID,Çalışkan Burcu2,Ark Mustafa1

Affiliation:

1. Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey

2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey

Abstract

Abstract 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.

Funder

Scientific Project Unit of Gazi University

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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