Synthesis and structure-activity relationships of N-benzyl-N-(X-2-hydroxybenzyl)-N'-phenylureas and thioureas as antitumor agents.
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.
Li
Huan-Qiu
HQ
State Key Laboratory of Pollution Control and Resource Reuse, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Yan
Tao
T
Yang
Ying
Y
Shi
Lei
L
Zhou
Chang-Fang
CF
Zhu
Hai-Liang
HL
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*
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D010671:Phenylurea Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D013890:Thiourea