Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines

Eur J Med Chem. 2014 Nov 24:87:140-9. doi: 10.1016/j.ejmech.2014.09.056.

Şeyma Cankara Pirol ¹, Burcu Çalışkan ¹, Irem Durmaz ², Rengül Atalay ³, Erden Banoglu ⁴

Affiliations

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey.
2 Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey.
3 Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey; Bilkent University Genetics and Biotechnology Research Center (BilGen), Bilkent University, 06800 Ankara, Turkey.
4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey. Electronic address: ebanoglu@gmail.com.

PMID: 25247770 DOI: 10.1016/j.ejmech.2014.09.056

Abstract

We synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and assessed their antiproliferative activities against three human Cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines) with the sulforhodamine B assay. Compound 4j with 2-chloro-4-pyridinyl group in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 1.6 μM, 3.3 μM and 1.1 μM for Huh7, MCF7 and HCT116 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G1 phase as an indicator of apoptotic cell death induction. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess potential in the design of more potent compounds for intervention with Cancer cell proliferation.

Keywords

Apoptosis; Autophagy; Cytotoxicity; Diarylpyrazole; Quinoline.

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