Novel hybrids from N-hydroxyarylamide and indole ring through click chemistry as histone deacetylase inhibitors with potent antitumor activities

Novel hybrid molecules 8a–8o were designed and synthesized by connecting indole ring with N-hydroxyarylamide through alkyl substituted triazole, and their in vitro biological activities were evaluated. It was discovered that most of target compounds showed promising anticancer activities, particularly for 8n, which had a significant HDACs inhibitory and antiproliferative activities comparable to or slightly stronger than SAHA against human carcinoma cells. Furthermore, compound 8n exhibited much better selectivity for HDAC1 over HDAC6 and HDAC8 than SAHA. In addition, compound 8n also could dose-dependently induce cancer cell cycling arrest at G0/G1 phase and promote the expression of the acetylation for histone H3 and tubulin in vitro. Therefore, our novel findings may provide a new framework for the design of new selective HDAC inhibitor for the treatment of cancer.

Novel hybrids 8a–8o were designed and synthesized, and most of them showed promising anti-cancer activities, particularly for 8n, which had significant antiproliferative activities and HDAC1 selectivity superior to SAHA, induced cell cycling arrest at G0/G1 phase, and promoted the expression of the acetylation for histone H3 and tubulin in vitro.Figure optionsDownload as PowerPoint slide