Discovery of nitroaryl urea derivatives with antiproliferative properties

0462783 - ÚEB 2017 RIV GB eng J - Journal Article
Wrobel, T.M. - Kielbus, M. - Kaczor, A.A. - Kryštof, Vladimír - Karczmarzyk, Z. - Wysocki, W. - Fruzinski, A. - Król, S. - Grabarska, A. - Stepulak, A. - Matosiuk, D.
Discovery of nitroaryl urea derivatives with antiproliferative properties.
Journal of Enzyme Inhibition and Medicinal Chemistry. Roč. 31, č. 4 (2016), s. 608-618. ISSN 1475-6366. E-ISSN 1475-6374
R&D Projects: GA ČR(CZ) GA15-15264S
Institutional support: RVO:61389030
Keywords : Antiproliferative * cancer * CDK inhibitor
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 4.293, year: 2016

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 mu M. 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.
Permanent Link: http://hdl.handle.net/11104/0262170