title: Synthesis and structure-activity relationships of N-benzyl-N-(X-2-hydroxybenzyl)-N'-phenylureas and thioureas as antitumor agents.
abstract: Two series of novel N-benzyl-N-(X-2-hydroxybenzyl)-N'-phenylureas and thioureas (1a-18a; 1b-18b) as potential EGFR and HER-2 kinase inhibitors have been discovered. These compounds displayed good EGFR and HER-2 inhibitory activity and the SARs are also been studied. Especially compound 7b demonstrated significant EGFR and HER-2 inhibitory activity (IC(50)=0.08 microM for EGFR and IC(50)=0.35 microM for HER-2). Docking simulation was performed to position compound 7b into the EGFR active site to determine the probable binding conformation and antiproliferative assay results indicating that these series of urea and thioureas own high antiproliferative activity against MCF-7. Above all, thiourea 7b would be a potential anticancer agent deserves further research.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Zhou
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D010671:Phenylurea Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D013890:Thiourea