Flavones have been known to inhibit growth of cancer cells. For the systematic studies to discover flavones showing cancer cell growth inhibitory effects, we prepared 36 synthetic flavone derivatives containing various substituent groups. The half-maximal cell growth inhibitory concentration (GI50) values of 36 flavone derivatives against HCT116 human colon cancer cell lines were determined and they ranged between 0.50 and 41.21 μM. Clonogenic long-term survival assay was used because this method can distinguish the cytotoxicities of the compounds with similar chemical structures. The structural conditions to show better cytotoxicity were derived based on the structure-activity relationships, and the pharmacophores obtained based on the CoMFA and CoMSIA models were addressed. In vitro kinase assay relating with cancer at the cellular level was performed. Of kinases tested, aurora kinase was inhibited effectively by synthesized flavone compounds. Western blotting analysis revealed that compound 31, which showed the best GI50 value, inhibited aurora kinases in a time-dependent manner as well as a dose-dependent manner. To elucidate the binding modes between compound 31 and aurora kinases at the molecular level, in silico docking experiments were also carried out.

Design, synthesis, and biological evaluation of flavones showing inhibitory effects on aurora kinases

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.