AUTHOR=Fu Lanlan , Mou Jiajia , Deng Yanru , Ren Xiaoliang , Qiu Shuang 

TITLE=Design, Synthesis, and Activity Assays of Cyclin-Dependent Kinase 1 Inhibitors With Flavone Scaffolds

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.940427

DOI=10.3389/fchem.2022.940427

ISSN=2296-2646

ABSTRACT=<p>Cyclin-dependent kinase 1 (CDK1) plays an indispensable role in the whole cell cycle. It has become a new target for cancer therapy. According to the binding mode of a pan-CDK inhibitor, flavopiridol with CDK1, and our previous work, a new series of flavone derivatives were discovered. Among them, compound <bold>2a</bold> showed the best CDK1 inhibitory and anti-proliferative potencies in the <italic>in vitro</italic> activity investigation. The IC<sub>50</sub> of <bold>2a</bold> against CDK1 was 36.42 ± 1.12 μM vs. 11.49 μM ± 0.56 of flavopiridol. In the anti-proliferation activity assays, <bold>2a</bold> exhibited better activity toward RAW264.7 than MCF-7 cells. The results indicated that flavone derivatives, besides inhibiting the growth of tumor cells, can also antagonize inflammatory response. Molecular docking results showed that conformation of <bold>2a</bold> can form hydrogen bonds and various hydrophobic interactions with the key amino acid residues of CDK1. It can be used as a promising lead compound for CDK1 inhibitor development.</p>