No 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 IC 50 values in the nano-molar range. The boronate ester 4 b was the most potent compound assessed in this study (IC 50 = 40.6 � 1.5 nM), followed closely by the 1,2-closo-carborane (IC 50 = 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.

The first examples of adenine binding by isomeric organoplatinum(II) complexes bearing Hbonding nicotinic and isonicotinic acid ligands are reported. Notably, a subtle switching of the H-bonding functionality from the 3-to 4-position of the pyridyl ring leads to a significant change in both the strength of association and the site of adenine binding.