title: Synthesis and evaluation of salicylanilide derivatives as potential epidermal growth factor receptor inhibitors.
abstract: 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.
authors: Anhui Key Laboratory of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230031, China.
authors: Minhua
authors: M
authors: Hu
authors: Wenfeng
authors: W
authors: Ye
authors: Jiaming
authors: J
authors: Li
authors: Guochen
authors: G
authors: Zhong
authors: Guangwei
authors: G
authors: He
authors: Qinlong
authors: Q
authors: Xu
authors: Yanchun
authors: Y
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012458:Salicylanilides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D013816:Thermodynamics
chemical_list: C000602517:4-(3-(piperidin-1-yl)propoxy)-N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012458:Salicylanilides; D066246:ErbB Receptors; C034596:salicylanilide; D000077156:Gefitinib
keywords: antiproliferative effects; epidermal growth factor receptor inhibitor; molecular modeling; salicylanilide derivatives