title: Additivity of molecular fields: CoMFA study on dual activators of PPARalpha and PPARgamma.
abstract: Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce the concept of additivity of molecular fields to correlate molecular fields of dual activators and their pIC(50) values. PPARalpha and PPARgamma dual activators, which affect hypertriglyceridemia and hyperglycemia, have been chosen to validate the molecular field additivity concept. Three CoMFA models namely alpha-model, gamma-model and dual-model have been developed. The validity of this concept has been ascertained by (a) comparing contour maps, (b) by comparing CoMFA results with FlexX docking results and (c) by analyzing newly designed molecules.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar, 160 062, Punjab.
authors.forename: Smriti
authors.initials: S
authors.lastname: Khanna
authors.forename: M E
authors.initials: ME
authors.lastname: Sobhia
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D001572:Benzofurans / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D010069:Oxadiazoles / Q000737:chemistry; D010078:Oxazines / Q000737:chemistry; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry*; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry
chemical_list: D001572:Benzofurans; D008024:Ligands; D010069:Oxadiazoles; D010078:Oxazines; D047493:PPAR alpha; D047495:PPAR gamma; D013844:Thiazoles