title: Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors.
abstract: A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC(50)=0.24μM for EGFR and IC(50)=1.07μM for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC(50) value of 0.30, 0.54, and 0.70μM, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Qiu
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Wang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Yang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases