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

Date
2014
Advisor
Instructor
Source Title
European Journal of Medicinal Chemistry
Print ISSN
0223-5234
Electronic ISSN
Publisher
Elsevier
Volume
87
Issue
Pages
140 - 149
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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 IC50values 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.

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Other identifiers
Book Title
Keywords
Apoptosis, Autophagy, Cytotoxicity, Diarylpyrazole, Quinoline, G1 phase
Citation
Published Version (Please cite this version)