title: Discovery of 4-aminoquinazoline--urea derivatives as Aurora kinase inhibitors with antiproliferative activity.
abstract: Two series of 20 novel 4-aminoquinazoline-urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry and The Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN 55414, USA.
authors.forename: Kwon Ho
authors.initials: KH
authors.lastname: Hong
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zong
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China; School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China. Electronic address: jimin@seu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Ji
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001549:Benzamides / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; C573775:4-aminoquinazoline; D000970:Antineoplastic Agents; D001549:Benzamides; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014508:Urea; D064096:Aurora Kinase A; D064107:Aurora Kinase B
keywords: Antiproliferative activity; Aurora kinase; Cancer cell; Docking simulation; Quinazolines; ZM447439