Common binding requirements of PPAR-α/δ/γ pan agonists: quantitative structure–activity relationship analysis of indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail group

Abstract

A QSAR study on a series of indanylacetic acid derivatives with activity against PPAR-α, δ, and γ was made using combination of various physiochemical descriptors. Several statistical regression expressions were obtained using stepwise multiple linear regression (MLR) analysis and partial least square (PLS) method. The highly predictive and validated models generated through classical 2D molecular descriptors provided deeper insights about the binding of these small molecules to the human nuclear receptor PPAR-α, δ, and γ. The results reveal that dipole moment and number of hydrogen bond donors are important descriptors in determining effective binding of PPAR agonists to all three subtypes.