Quantitative structure activity analysis of 2-alkoxydihydrocinnamates as PPARalpha/gamma dual agonist.
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.
Kumar
P Manoj
PM
Molecular Modeling Study group, Mahakal Institute of Pharmaceutical Studies, Ujjain -456664, Madhya Pradesh, India. mkmph7931@gmail.com
Hemalatha
R
R
Mahajan
S C
SC
Karthikeyan
C
C
Moorthy
N S Hari Narayana
NS
Trivedi
Piyush
P
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
D002934:Cinnamates; D047493:PPAR alpha; D047495:PPAR gamma