Diarylcyclopropane hydroxamic acid inhibitors of histone deacetylase 4 designed by combinatorial approach and QM/MM calculations

Computer-assisted combinatorial chemistry, molecular mechanics and hybrid QM/MM (DFT-B3LYP/6-31G*//OPLS-2005) approach with implicit solvent model were used to design and optimize diarylcyclopropane hydroxamic acid inhibitors of histone deacetylase 4, which are involved in a number of indications including cancer, Huntington's disease, Alzheimer's disease, muscular atrophy, metabolic disorders, acute ischemic injury and inflammation.264