title: 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.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey.
authors.forename: Şeyma
authors.initials: Ş
authors.lastname: Cankara Pirol
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Çalışkan
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey.
authors.forename: Irem
authors.initials: I
authors.lastname: Durmaz
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey; Bilkent University Genetics and Biotechnology Research Center (BilGen), Bilkent University, 06800 Ankara, Turkey.
authors.forename: Rengül
authors.initials: R
authors.lastname: Atalay
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey. Electronic address: ebanoglu@gmail.com.
authors.forename: Erden
authors.initials: E
authors.lastname: Banoglu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002264:Carboxylic Acids / Q000737:chemistry*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000737:chemistry*; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011720:Pyrazoles; D015363:Quinolones; C031280:pyrazole
keywords: Apoptosis; Autophagy; Cytotoxicity; Diarylpyrazole; Quinoline