RESUMO
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±1.5â nM), followed closely by the 1,2-closo-carborane (IC50 =42.9±1.5â nM). Compound 4 b exceeds the potency of the related gold-standard HDAC pan-inhibitor vorinostat (1) toward this particular HDAC isoform.
Assuntos
Compostos de Boro/farmacologia , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Compostos de Boro/síntese química , Compostos de Boro/química , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Estrutura MolecularRESUMO
We report the first example of an ionic graphene salt containing boron. An anionic charge is introduced to the graphene surface by means of 7,8-nido-[C2B9H11](-) carborane clusters covalently and electronically bound to the graphene lattice, and this new material was isolated as its Cs(+) salt.
RESUMO
The conjugated aromatic system of graphene was used to trap the reactive, boron-rich 1,2-carborane cluster. Functionalization of the graphene surface was confirmed by solid-state MAS (11)B NMR spectroscopy and quantified by X-ray photoelectron spectroscopy. This work represents the first confirmed example of direct functionalization of a graphene lattice with carboranes.
