BioScience Trends. 2019;13(3):267-272. (DOI: 10.5582/bst.2019.01054)

Design and synthesis of novel histone deacetylase 6 inhibitors with benzyl-triazole as the core skeleton.

Mou ZS, Gao JJ, Miao H, Zhang L, Su L, Wang BL, Luan YP


In the field of epigenetics, histone deacetylases (HDACs) are important members and well validated targets for anti-cancer drugs discovery. In this study, we designed and synthesized twenty-seven novel hydroxamic acid-based HDAC inhibitors (HDACis) with benzyl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward HDACs. Among them, compounds ZM-22 to ZM-27 with inhibition rates more than 90% toward HDACs exhibited potent inhibitory activity toward HDAC6, and ZM-23 possessed the best selectivity to HDAC6 over HDAC1. The high potency of compound ZM-23 toward HDAC6 was rationalized by molecular docking simulation. This series of compounds is worthy for further anti-cancer activity evaluation and structural optimization works.

KEYWORDS: Histone deacetylase, isoform, selective, inhibitor, anti-tumor

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