Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives.
Eman S NossierSomaia S Abd El-KarimNagy M KhalifaAli S El-SayedEmad S I HassanSalwa M El-HalloutyPublished in: Molecules (Basel, Switzerland) (2018)
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 6 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, p38α and PDGFRβ at 100 μM 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 6 is a potential agent for cancer therapy deserving further research.
Keyphrases
- molecular docking
- tyrosine kinase
- high throughput
- molecular dynamics simulations
- cancer therapy
- protein kinase
- signaling pathway
- cell proliferation
- small cell lung cancer
- epidermal growth factor receptor
- papillary thyroid
- drug delivery
- single cell
- risk assessment
- squamous cell carcinoma
- lymph node metastasis
- cell death
- amino acid
- climate change
- wild type
- cell cycle arrest