title: Prospective QSAR-Based Prediction Models with Pharmacophore Studies of Oxadiazole-Substituted α-Isopropoxy Phenylpropanoic Acids with Dual Activators of PPARα and PPARγ.
abstract: A series of oxadiazole-substituted [Formula: see text]-isopropoxy phenylpropanoic acids with dual activators of PPARα and PPARγ derivatives were subjected to two-dimensional and k-Nearest Neighbors molecular field analysis. The statistically significant best 2D-QSAR (PPARα ) model having good predictive ability with statistical values of r(2) = 0:8725; q(2) = 0:7957and pred_r(2) = 0:8136 was developed by GA-PLS with the descriptors like SsClcount, SddsN (nitro) count and SsOHcount that contribute significantly to the biological activity. The best 3D-QSAR studies (PPARα ) were performed using the genetic algorithm selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q(2) = 0:7188 and predicate activity pred_r(2) = 0.7508 were obtained. The influences of steric and electrostatic field effects generated by the contribution plots are discussed. The best pharmacophore model includes three features, viz. hydrogen bond donor, hydrogen bond acceptor and aromatic features. The information rendered by 2D-QSAR and 3D-QSAR models may lead to a better understanding of structural requirements of substituted α-isopropoxy phenylpropanoic derivatives and also aid in designing novel potent PPARα and PPARγ for antihyperglycemic molecules.
authors.affiliation: Drug Design and Development Laboratory, School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshila Campus, Khandwa Road, Indore, 452 001, MP, India. mukeshcsharma@yahoo.com.
authors.forename: Mukesh C
authors.initials: MC
authors.lastname: Sharma
mesh_terms: D010069:Oxadiazoles / Q000737:chemistry*; D047493:PPAR alpha / Q000737:chemistry*; D047495:PPAR gamma / Q000737:chemistry*; D010666:Phenylpropionates / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D010069:Oxadiazoles; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; C538759:alpha-isopropoxy phenylpropanoic acid
keywords: 2D-QSAR; Antihyperglycemic; PPAR; Pharmacophore; Phenylpropanoic; VLife MDS; k-Nearest neighbor