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

Abstract

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.

In vitroanticancer potentiality and molecular modelling study of novel amino acid derivatives based onN1,N3-bis-(1-hydrazinyl-1-oxopropan-2-yl) isophthalamide

“…Docking simulations were done using Molecular Operating Environment software 10.2008 (MOE), Chemical Computing Group Inc., Montreal, Quebec, Canada 42 . The X-ray crystallographic structure of EGFR (pdb code: 1M17) 43 was downloaded from the protein data bank with its ligand, erlotinib. The docking protocol was validated by re-docking the co-crystallized ligand, erlotinib into the EGFR binding pocket, followed by docking of our compound 5 in the same binding site.…”

“…The molecular modelling of the compound 5 was carried out using molecular operating environment (MOE, 10.2008) software 42 . The X-ray crystallographic structure of EGFR co-crystallized with erlotinib as an inhibitor (PDB ID: 1M17) 43 was downloaded from the protein data bank. The receptor was prepared for docking study using Protonate 3D protocol in MOE with default options followed by water molecules removal.…”

Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors

“…The molecular docking simulation study was performed using Molecular Operating Environment (MOE ® ) 2008.10 software [45]. The crystal structures of E. coli topoisomerase II DNA gyrase B complexed with their ligands novobiocin (PDB code: 1AJ6) [37,38] was retrieved from the Protein Data Bank.…”

Design, Synthesis and Molecular Docking Studies of Novel Cyclic Pentapeptides Based on Phthaloyl Chloride with Expected Anticancer Activity

“…Molecular docking studies The molecular modeling of the compound 3 was carried out using Molecular Operating Environment (MOE, 10.2008) software [44]. The X-ray crystallographic structure of EGFR cocrystallized with erlotinib as inhibitor (PDB ID: 1M17) [45] was downloaded from the protein data bank. The receptor was prepared for docking study using Protonate 3D protocol in MOE with default options followed by water molecules removal.…”