title: Synthesis and antiproliferative activities against Hep-G2 of salicylanide derivatives: potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase.
abstract: A series of salicylanilide derivatives (compounds 1-32) were synthesised by reacting substituted salicylic acids and anilines. The chemical structures of these compounds were determined by (1)H-NMR, electrospray ionisation mass spectrometry (ESI-MS) and elemental analysis. The compounds were assayed for their antiproliferative activities against the Hep-G2 cell line by the 3-(4,5-dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Among the compounds tested, 22 and 28 showed the most favouable antiproliferative activities with 50% inhibitory concentration (IC(50)) values of 1.7 and 1.3 μM, respectively, which were comparable to the positive control of 5-fluorouracil (IC(50)=1.8 μM). A solid-phase ELISA assay was also performed to evaluate the ability of compounds 1-32 to inhibit the autophosphorylation of the epidermal growth factor receptor tyrosine kinase (EGFR TK). Docking simulations of 22 and 28 were carried out to illustrate the binding mode of the molecule into the EGFR active site, and the result suggested that both compounds 22 and 28 could bind the EGFR kinase well.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ruan
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Suo-Ping
authors.initials: SP
authors.lastname: Xu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005472:Fluorouracil / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011485:Protein Binding; D012458:Salicylanilides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012459:Salicylates / Q000737:chemistry; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000032:analysis; D013844:Thiazoles / Q000032:analysis
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D012458:Salicylanilides; D012459:Salicylates; D013778:Tetrazolium Salts; D013844:Thiazoles; D066246:ErbB Receptors; C022616:thiazolyl blue; C023650:aniline; D005472:Fluorouracil