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
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.87, ss.140-149, 2014 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 87
- Basım Tarihi: 2014
- Doi Numarası: 10.1016/j.ejmech.2014.09.056
- Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.140-149
- Anahtar Kelimeler: Diarylpyrazole, Quinoline, Cytotoxicity, Autophagy, Apoptosis, BIOLOGICAL EVALUATION, PYRAZOLE DERIVATIVES, HYDRAZONE DERIVATIVES, DISCOVERY, APOPTOSIS, AUTOPHAGY, INHIBITORS, AGENTS, LC3
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Gazi Üniversitesi Adresli: Evet
Özet
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 mu M, 3.3 mu M and 1.1 mu M 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. (C) 2014 Elsevier Masson SAS. All rights reserved.