title: Discovery of nitroaryl urea derivatives with antiproliferative properties.
abstract: A series of urea derivatives bearing nitroaryl moiety has been synthesized and assayed for their potential antiproliferative activities. Some of the tested compounds displayed activity in RK33 laryngeal cancer cells and TE671 rhabdomyosarcoma cells while being generally less toxic to healthy HSF human fibroblasts cells. One compound was demonstrated to be a moderate CDK2 inhibitor with IC50 = 14.3 µM. Its structure was solved by an X-ray crystallography and molecular modelling was performed to determine structure-activity relationship. Obtained compounds constitute novel structures and generally demonstrated greater cytotoxicity in comparison to cisplatin. This study offers new structural motifs with potential for further development.
authors.affiliation: a Department of Synthesis and Chemical Technology of Pharmaceutical Substances and.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Wróbel
authors.affiliation: b Department of Biochemistry and Molecular Biology , Medical University of Lublin , Lublin , Poland .
authors.forename: Michał
authors.initials: M
authors.lastname: Kiełbus
authors.affiliation: a Department of Synthesis and Chemical Technology of Pharmaceutical Substances and.|c School of Pharmacy, University of Eastern Finland , Kuopio , Finland .
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.affiliation: d Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacký University , Olomouc , Czech Republic .
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kryštof
authors.affiliation: e Department of Chemistry , Siedlce University of Natural Sciences and Humanities , Siedlce , Poland , and.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Karczmarzyk
authors.affiliation: e Department of Chemistry , Siedlce University of Natural Sciences and Humanities , Siedlce , Poland , and.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wysocki
authors.affiliation: f Institute of General and Ecological Chemistry, Technical University of Lodz , Lodz , Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fruziński
authors.affiliation: b Department of Biochemistry and Molecular Biology , Medical University of Lublin , Lublin , Poland .
authors.forename: Sylwia K
authors.initials: SK
authors.lastname: Król
authors.affiliation: b Department of Biochemistry and Molecular Biology , Medical University of Lublin , Lublin , Poland .
authors.forename: Aneta
authors.initials: A
authors.lastname: Grabarska
authors.affiliation: b Department of Biochemistry and Molecular Biology , Medical University of Lublin , Lublin , Poland .
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stepulak
authors.affiliation: a Department of Synthesis and Chemical Technology of Pharmaceutical Substances and.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Matosiuk
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D014508:Urea; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Antiproliferative; CDK inhibitor; cancer; molecular modelling; synthesis