title: Exploring molecular fingerprints of selective PPARδ agonists through comparative and validated chemometric techniques.
abstract: Peroxysome proliferator-activated receptors (PPARs) have grown greatly in importance due to their role in the metabolic profile. Among three subtypes (α, γ and δ), we here consider the least investigated δ subtype to explore the molecular fingerprints of selective PPARδ agonists. Validated QSAR models (regression based 2D-QSAR, HQSAR and KPLS) and molecular docking with dynamics analyses support the inference of classification-based Bayesian and recursive models. Chemometric studies indicate that the presence of ether linkages and heterocyclic rings has optimum influence in imparting selective bioactivity. Pharmacophore models and docking with molecular dynamics analyses postulate the occurrence of aromatic rings, HB acceptor and a hydrophobic region as crucial molecular fragments for development of PPARδ modulators. Multi-chemometric studies suggest the essential structural requirements of a molecule for imparting potent and selective PPARδ modulation.
authors.affiliation: a Department of Chemical Technology , University of Calcutta , Kolkata , India.
authors.forename: A
authors.initials: A
authors.lastname: Nandy
authors.forename: K
authors.initials: K
authors.lastname: Roy
authors.forename: A
authors.initials: A
authors.lastname: Saha
mesh_terms: D001499:Bayes Theorem; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047494:PPAR delta
keywords: 2D-QSAR; HQSAR; KPLS; PPAR; dynamics; pharmacophore