Design, synthesis, and antitumor activity evaluation of carbazole derivatives with potent HDAC inhibitory activity

In this study, we designed and synthesized a series of novel carbazole-hydroxamate analogues as HDAC inhibitors and evaluated their anti-tumor properties in vitro. Compared with vorinostat, the HDAC semi-inhibitory concentration of compounds3f and3g decreased 4 –13 folds, compounds8a and8c also showed strong inhibitory HDAC activity, and compound3g had a strong inhibitory effect on HDAC 1. The CCK8 assay showed that compounds3g displayed good antiproliferative activity on tested tumor cells. Flow cytometric and western blot assay showed that3g exerted anti-tumor activities by regulating the level of Ac-HH3 and activating the cleaved caspase 3. Based on these results, carbazole-hydroxamate derivative3g might become a potential anti-tumor candidate molecule to further structural optimization research.Graphical Abstract
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research