title: Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.
abstract: BACKGROUND
  Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells.
  
  
  OBJECTIVE
  To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies.
  
  
  METHODS
  The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with wellassigned HDAC inhibitory activity were used for 3D-QSAR model development.
  
  
  RESULTS
  Best 3D-QSAR model, which is a five partial least square (PLS) factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross-validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation (0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a 3D query for virtual screening against the ZINC database. In the virtual screening workflow, docking studies (HTVS, SP and XP) were carried out by selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10, 1W22). Finally, six compounds were obtained based on high scoring function (dock score -11.2278-10.2222 kcal/mol) and diverse structures.
  
  
  CONCLUSIONS
  The structure activity correlation was established using virtual screening, docking, energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models and their validation. The outcomes of these studies could be further employed for the design of novel HDAC inhibitors for anticancer activity.
authors.forename: Preeti
authors.initials: P
authors.lastname: Patel
authors.forename: Avineesh
authors.initials: A
authors.lastname: Singh
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Patel
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Jain
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Veerasamy
authors.affiliation: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495009, India. harishdops@yahoo.co.in.
authors.forename: Harish
authors.initials: H
authors.lastname: Rajak
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003198:Computer Simulation; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors