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Discovery of nitroaryl urea derivatives with antiproliferative properties |
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| Authors: | Tomasz M. Wróbel Michał Kiełbus Agnieszka A. Kaczor Vladimír Kryštof Zbigniew Karczmarzyk Waldemar Wysocki |
| Affiliation: | 1. Department of Synthesis and Chemical Technology of Pharmaceutical Substances and tomasz.wrobel@umlub.pl;3. Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland,;4. Department of Synthesis and Chemical Technology of Pharmaceutical Substances and;5. School of Pharmacy, University of Eastern Finland, Kuopio, Finland,;6. Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR &7. Palacky University, Olomouc, Czech Republic,;8. Department of Chemistry, Siedlce University of Natural Sciences and Humanities, Siedlce, Poland, and |
| 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. |
| Keywords: | Antiproliferative cancer CDK inhibitor molecular modelling synthesis |