piperidines and salicylanilide

Two series of novel salicylanilide were synthesized as potential epidermal growth factor receptor (EGFR) inhibitors. The enzyme inhibitory activity against EGFR of all compounds was carried out, and their antiproliferative activities against the A549 and A431 cell lines were also evaluated. Of the compounds studied, majority of them exhibited high antiproliferative activities compared with gefitinib; especially, 12a and 12b exhibited stronger inhibitory activity against EGFR with IC50 values of 10.4 ± 2.25 and 15.4 ± 2.33 nm, respectively, which were comparable to the positive control of gefitinib (IC50 = 12.1 ± 2.21 nm). Compound 12b also showed outstanding inhibitory activity against A431 and A549 cell lines with the IC50 values of 0.42 ± 0.43 μm and 0.57 ± 0.43 μm, which was better than the positive controls. In the molecular modeling study, compound 12b was bound into the active pocket of EGFR with two hydrogen bond and with minimum binding free energy ▵Gb = -25.1125 kcal/mol. The result also suggested that compound 12b could bind the EGFR kinase well.

Topics: Antineoplastic Agents; Benzamides; Binding Sites; Cell Line, Tumor; Cell Proliferation; ErbB Receptors; Gefitinib; Humans; Hydrogen Bonding; Molecular Docking Simulation; Piperidines; Protein Binding; Protein Kinase Inhibitors; Protein Structure, Tertiary; Quinazolines; Salicylanilides; Thermodynamics

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Piperidines; Salicylanilides; Tinea