Discovery of novel potential selective HDAC8 inhibitors by combine ligand-based, structure-based virtual screening and in-vitro biological evaluation.

ABSTRACT: Neuroblastoma is the most common extracranial solid tumor found in children and survival rate is extremely meager. HDAC8, a class I zinc-dependent enzyme, is a potential drug target for treatment of neuroblastoma and T cell lymphoma. Most of the HDAC8 inhibitors discovered till date contains a hydroxamic acid group which acts as a zinc binding group. The high binding affinity to the zinc and other ions results in adverse effects. Also, the non-selective inhibition of HDACs cause a variety of side effects. The objective of this is to identify structurally diverse, non-hydroxamate, novel, potential and selective HDAC8 inhibitors. A number of five featured pharmacophore hypotheses were generated using 32 known selective HDAC8 inhibitors. The hypotheses ADDRR.4 were selected for building 3D QS

SUBMITTER: Debnath S 

PROVIDER: S-EPMC6868012 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature