Discovery of nitroaryl urea derivatives with antiproliferative properties

0462783 - ÚEB 2017 RIV GB eng J - Článek v odborném periodiku
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
Grant CEP: GA ČR(CZ) GA15-15264S
Institucionální podpora: RVO:61389030
Klíčová slova: Antiproliferative * cancer * CDK inhibitor
Kód oboru RIV: FR - Farmakologie a lékárnická chemie
Impakt faktor: 4.293, rok: 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.
Trvalý link: http://hdl.handle.net/11104/0262170