Department of Chemistry and Technology of Biomedical Drugs, Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 Moscow, Russia.
Molecules. 2022 Jun 4;27(11):3616. doi: 10.3390/molecules27113616.
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 HO and CoCl 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 CoCl 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.
天然细胞因子是一组有前途的细胞保护和抗肿瘤药物。在这项研究中，我们合成了一组带有烷基和氯取代基的芳基氨基甲酸酯、吡啶基脲和芳基脲细胞因子类似物，并测试了它们在 MDA-MB-231、A-375 和 U-87 MG 细胞系中的抗增殖活性，以及在 HO 和 CoCl 模型中的细胞保护特性。带有草酰氨基部分的芳基氨基甲酸酯对测试的癌细胞系具有选择性的增殖抑制作用，而芳基脲则没有活性。在细胞保护研究中，相同的芳基氨基甲酸酯能够抵消 CoCl 的细胞毒性 3-8%。在抗增殖作用中，芳基氨基甲酸酯的可能分子靶标是腺苷 A2 受体和 CDK2。获得的结果为开发新型抗癌疗法提供了希望。
