Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents
Maxim Oshchepkov,
Leonid Kovalenko,
Antonida Kalistratova,
Maria Ivanova,
Galina Sherstyanykh,
Polina Dudina,
Alexey Antonov,
Anastasia Cherkasova,
Mikhail Akimov
Affiliations
Maxim Oshchepkov
Department of Chemistry and Technology of Biomedical Drugs, Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
Leonid Kovalenko
Department of Chemistry and Technology of Biomedical Drugs, Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
Antonida Kalistratova
Department of Chemistry and Technology of Biomedical Drugs, Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
Maria Ivanova
Department of Chemistry and Technology of Biomedical Drugs, Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, 125047 Moscow, Russia
Galina Sherstyanykh
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 Moscow, Russia
Polina Dudina
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 Moscow, Russia
Alexey Antonov
Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, 119991 Moscow, Russia
Anastasia Cherkasova
Faculty of Biotechnology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, 119991 Moscow, Russia
Mikhail Akimov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 Moscow, Russia
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.
