Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron

Abstract

Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour‐suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron‐based (boronic acid, boronate ester and closo‐1,2‐carborane) HDAC2 inhibitors with IC50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC50=40.6±1.5 nM), followed closely by the 1,2‐closo‐carborane (IC50=42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold‐standard HDAC pan‐inhibitor vorinostat (1) toward this particular HDAC isoform.