Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents

Abstract

Natural cytokinines are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of aryl carbamate, pyridyl urea, and aryl urea cytokinine analogs with alkyl and chlorine substitutions and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Aryl carbamates with the oxamate moiety were selectively anti-proliferative for the cancer cell lines tested, while the aryl ureas were inactive. In the cytoprotection studies, the same aryl carbamates were able to counteract the CoCl2 cytotoxicity by 3–8%. The possible molecular targets of the aryl carbamates during the anti-proliferative action were the adenosine A2 receptor and CDK2. The obtained results are promising for the development of novel anti-cancer therapeutics.

Keywords

• carbamates
• oxamates
• synthetic cytokinins
• substituted ureas
• anti-stress effect
• cytotoxicity