Targeting epigenetic regulator histone deacetylase 6 in the treatment of cancer cancer: a computational approach

Abstract

Targeting the, chromatin modifying enzyme, Histone deacetylase 6 has been a strategy that is recently identified to treat several cancers such as liver, lung and other tumours. Besides deacetylating histones, the enzyme also acts on proteins such as HSP90, Cortactin and á-tubulin that are involved in tumorigenesis. The present study combines the techniques of structure based and ligand based virtual screening methods to identify new drug compounds that could selectively inhibit HDAC6. The second catalytic domain of the enzyme was modelled and docking studies were performed on it with the compounds obtained from literature. The results of the docking were employed to screen the compounds for building a pharmacophore model. The Pharmacophore model was utilized in identifying 106 compounds from drugbank as hits. A genetic algorithm based QSAR model was developed to further screen the hits identified to 58 based on predicted activity. Free binding energy estimation was done for the 58 compounds and the poses with best binding energy and interactions are suggested as inhibitors of histone deacetylase 6.