Journal of Enzyme Inhibition and Medicinal Chemistry 2016-08-01

Discovery of nitroaryl urea derivatives with antiproliferative properties.

Tomasz M Wróbel, Michał Kiełbus, Agnieszka A Kaczor, Vladimír Kryštof, Zbigniew Karczmarzyk, Waldemar Wysocki, Andrzej Fruziński, Sylwia K Król, Aneta Grabarska, Andrzej Stepulak, Dariusz Matosiuk

文献索引：J. Enzyme Inhib. Med. Chem. , 1-11, (2015)

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摘要

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.