Design, synthesis, anticancer evaluation and molecular docking study of novel 2,4-dichlorophenoxymethyl-based derivatives linked to nitrogenous heterocyclic ring systems as potential CDK-2 inhibitors

Synthesis and biological evaluation of new derivatives of thieno-thiazole and dihydrothiazolo-thiazole scaffolds integrated with a pyrazoline nucleus as anticancer and multi-targeting kinase inhibitors

“…This study was done using MOE-Dock (Molecular Operating Environment) software version 2014.0901. 70–72 The docking process was first validated through self-docking of the co-crystallized ligands erlotinib, sorafenib and SB-590885 within the active sites of EGFR, VEGFR-2 and BRAF V600E (PDB codes: , and , respectively) 73–75 giving energy scores of −12.23, −11.50 and −11.37 kcal mol −1 with small RMSD values of 0.88, 1.24 and 1.35 Å, respectively between the co-crystallized ligands and their docked poses.…”

“…The protonated 3D was employed using standard bond lengths and angles, using Molecular Operating Environment (MOE-Dock) software version 2014.0901. 70–72 Then, the geometry optimization and energy minimization were applied to get the Conf Search module in MOE, followed by saving of the MOE file for upcoming docking process. The co-crystallized structures of EGFR, VEGFR-2 and BRAF V600E kinases with their ligands erlotinib, sorafenib and SB-590885 were downloaded (PDB codes: , and , respectively) from protein data bank.…”

Novel 1,2,3-Triazole-Coumarin Hybrid Glycosides and Their Tetrazolyl Analogues: Design, Anticancer Evaluation and Molecular Docking Targeting EGFR, VEGFR-2 and CDK-2

“…In order to identify the possible anticancer mechanisms of the promising synthesized targets 10 , 13 and 15 , kinase profiling assessment was estimated against EGFR, VEGFR-2 and CDK-2/cyclin A2 using erlotinib, sorafenib and roscovitine as standard drugs, respectively [ 5 , 64 , 65 ]. The kinase inhibitory data are depicted as IC 50 values (μM) in Table 3 .…”

“…Based upon the kinase inhibitory results of the targets 10 , 13 and 15 , the docking simulation study was conducted in attempt to provide a correlation between their activities and the possible binding modes and orientations within the binding sites of EGFR, VEGFR-2 and CDK-2/cyclin A2 kinases. The docking process was applied using MOE-Dock (Molecular Operating Environment) software version 2014.0901 [ 68 , 69 , 70 ] and validated through re-docking of the native ligands erlotinib, sorafenib and roscovitine within the active sites of EGFR, VEGFR-2 and CDK-2/cyclin A2 (PDB codes: 1M17, 4ASD and 3DDQ, respectively) [ 65 , 71 , 72 ] giving energy scores of −12.10, −11.59 and −11.25 kcal/mol with small RMSD values of 0.88, 1.20 and 0.77 Å, respectively, between the co-crystallized ligands and their docked poses.…”

“…The targets with promising cytotoxicity 10 , 13 and 15 were evaluated for their in vitro inhibitory activity against EGFR, VEGFR-2 and CDK-2/cyclin A2 using erlotinib, sorafenib and roscovitine as references, respectively, following the previously mentioned procedure [ 5 , 64 , 65 ].…”