Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives

• Main Authors: Eman S. Nossier, Somaia S. Abd El-Karim, Nagy M. Khalifa, Ali S. El-Sayed, Emad S. I. Hassan, Salwa M. El-Hallouty
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: Molecules
• Subjects: triarylpyrazole derivatives; triazolo[1,5-<i>a</i>]pyridines; anticancer activity; EGFR; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/23/12/3074
• ISSN: 1420-3049

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound <b>6</b> showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38&#945; and PDGFR&#946; at 100 &#956;M using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound <b>6</b> is a potential agent for cancer therapy deserving further research.