title: Computational identification of novel histone deacetylase inhibitors by docking based QSAR.
abstract: Histone deacetylases (HDACs) are enzymes that modify chromatin structure and contribute to aberrant gene expression in cancer. A series compounds with well-assigned HDAC inhibitory activity was used for docking based 3D-QSAR analysis. The 3D-QSAR acquired had excellent correlation coefficient value (q2=0.753) and high Fisher ratio (F=300.2). A validated pharmacophore model (AAAPR) was employed for virtual screening. After manual selection, molecular docking and further refinement, six compounds with good absorption, distribution, metabolism, and excretion (ADME) properties were selected as potential HDAC inhibitors. Further, the molecular interactions of these inhibitors with the HDAC active site residues were discussed in detail.
authors.affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut 673601, Kerala, India.
authors.forename: Syam B
authors.initials: SB
authors.lastname: Nair
authors.forename: Mahesh Kumar
authors.initials: MK
authors.lastname: Teli
authors.forename: H
authors.initials: H
authors.lastname: Pradeep
authors.forename: G K
authors.initials: GK
authors.lastname: Rajanikant
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D012044:Regression Analysis; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056572:Histone Deacetylase Inhibitors; D007093:Imidazoles; C029899:imidazole; C031000:benzimidazole; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2