title: Design, synthesis, and biological evaluation of imidazoline derivatives as p53-MDM2 binding inhibitors.
abstract: Three series of novel imidazoline derivatives were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory activities, and anti-proliferation activities against PC3, A549, KB, and HCT116 cancer cell lines. Five of the tested compounds showed enhanced p53-MDM2 binding inhibitory potency and anti-proliferation activities in comparison with that of Nutlin-1. Flow cytometric analysis indicated that compound 7c, one of the most potent p53-MDM2 binding inhibitors with a K(i) value of 0.6 μM, showed its ability to arrest cell cycle progression.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Chunqi
authors.initials: C
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Weisi
authors.initials: W
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Lulu
authors.initials: L
authors.lastname: Tao
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Rong
authors.initials: R
authors.lastname: Sheng
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D048288:Imidazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D048288:Imidazolines; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2