title: Quantitative structure activity analysis of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist.
abstract: To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave-one-out cross validation method. Analyses of results from the present QSAR study suggest that for favorable dual PPARalpha/gamma agonist activity electronic property of the substituents in hydrophobic tail phenyl ring plays a key role. The contribution of Hammett constant and dipole moment in the models deduced the importance of electron withdrawing substituents for dual activity. Additionally the study also indicates that bulky substituents in head acid moiety not confer selectivity towards the PPAR activity. Thus the QSAR study brings important structural insight to aid the design of dual PPARalpha/gamma receptor agonist.
authors.affiliation: Molecular Modeling Study group, Mahakal Institute of Pharmaceutical Studies, Ujjain -456664, Madhya Pradesh, India. mkmph7931@gmail.com
authors.forename: P Manoj
authors.initials: PM
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Hemalatha
authors.forename: S C
authors.initials: SC
authors.lastname: Mahajan
authors.forename: C
authors.initials: C
authors.lastname: Karthikeyan
authors.forename: N S Hari Narayana
authors.initials: NS
authors.lastname: Moorthy
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D002934:Cinnamates / Q000737:chemistry*; D016014:Linear Models; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D002934:Cinnamates; D047493:PPAR alpha; D047495:PPAR gamma