Anti-Proliferative and Cytoprotective Activity of Ethylenediurea Derivatives with Alkyl and Oxygen-containing Groups as Substituents

Maxim S. Oshchepkov; Leonid Kovalenko; Antonida Kalistratova; Galina Sherstyanykh; Evgenia Gorbacheva; Alexey Antonov; Karina Ustinova; Nisreen Khadour; and Mikhail Akimov

doi:10.20944/preprints202405.1732.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 27 May 2024 / Approved: 27 May 2024 / Online: 27 May 2024 (10:27:42 CEST)

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, 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. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

carbamates; oxamates; synthetic cytokinins; substituted ureas; anti-oxidative effect; cytotoxicity; oxidative stress

Chemistry and Materials Science, Medicinal Chemistry

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Anti-Proliferative and Cytoprotective Activity of Ethylenediurea Derivatives with Alkyl and Oxygen-containing Groups as Substituents

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