title: Common SAR Derived from Multiple QSAR Models on Vorinostat Derivatives Targeting HDACs in Tumor Treatment.
abstract: Dysregulation of HDACs has been associated with tumour development and therefore inhibiting HDAC's have surfaced as promising therapeutic strategy in malignancy.
  
  
  
  Vorinostat analogues with different biological activities were investigated for underlying structure-activity relationship.
  
  
  
  Out of six activities and their multiple QSAR models, HDAC1 and HDAC8 produced statistically fit, stable and predictive linear (MLR) and non-linear (SVM) QSAR models. In case of HDAC1 activity as end point, linear (R2=0.8089, R2 CV=0.7343) and non-linear (R2=0.9801, R2 CV=0.8952) QSAR models turned reliable to investigate SAR. Similarly, HDAC8 activity based linear (R2=0.9454, R2 CV=0.9049) and non-linear (R2=0.9899, R2 CV=0.9232) QSAR models produced statistically improved and stable models.
  
  
  
  Molecular descriptors derived from 3-D Morse and Radial Distribution Function indices were found to be selective in all the models. These molecular descriptors which encode common SAR among Vorinostat derivatives were evaluated for their potent HDAC inhibition activity.
authors.forename: Sugathan
authors.initials: S
authors.lastname: Praseetha
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
authors.forename: Mukesh
authors.initials: M
authors.lastname: Yadav
authors.forename: Anuraj
authors.initials: A
authors.lastname: Nayarisseri
authors.affiliation: Research and Development Centre, Bharathiyar University, Coimbatore, 641046, India. suresh@kufos.ac.in.
authors.forename: Sivanpillai
authors.initials: S
authors.lastname: Sureshkumar
mesh_terms: D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012097:Repressor Proteins; D000077337:Vorinostat; C110550:HDAC1 protein, human; C409470:HDAC8 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases