5-Hydroxyindole-Based EZH2 Inhibitors Assembled via TCCA-Catalyzed Condensation and Nenitzescu Reactions.

ABSTRACT: 5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L-04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC₅₀ = 52.6 μM). These findings revealed that compound L-04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we

SUBMITTER: Du F 

PROVIDER: S-EPMC7248849 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature