Structure-based drug designing of histone deacetylase-2 inhibitors as anticancer agents

Abstract

Histone deacetylase 2 (HDAC-2) in tumor development and carcinogenesis is a promising therapeutic target for cancer treatment. HDAC-2 belongs to class I histone deacetylase and acts as a transcriptional repressor through the deacetylation of lysine residues present at the N-terminal tail of histone proteins (H2A, H2B, H3, and H4). They are overexpressed in various solid tumors like cutaneous T cell lymphoma, colorectal cancer, prostate cancer, lung cancer, breast cancer, gastric cancer, liver cancer, and medulloblastoma. Hence, targeting HDAC-2 could be a rewarding strategy to combat cancer. The goal of the research is to design, develop, and identify molecules through docking, Ligplot, ADMET properties, and molecular dynamic studies. The compound CHEMBL4087539 has been observed to be a top scoring inhibitor against HDAC-2. The molecular dynamics simulation shows the convergence of ligand protein interaction. In the 100 ns, the ligand strongly interacts with HDAC-2. Furthermore, the ADME studies show the suitability of predicted inhibitor as a drug like molecule.