QSAR rationales for the PPARα/γ agonistic activity of 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline derivatives

The PPARγ binding affinity and transactivation profiles for hPPARα and hPPARγ of tetrahydroquinoline derivatives have been quantitatively analyzed in terms of topological 0D-, 1D- and 2D-descriptors based on molecular graph theory. Statistically sound models have been obtained between the biological actions and various DRAGON descriptors through combinatorial protocol-multiple linear regression (CP-MLR) computational procedure. Amongst the large number of such derived models, the most significant ones have only been discussed to draw meaningful conclusions. From the statistically significant models, it appeared that the mode of actions of titled compounds were different for hPPARα and hPPARγ transactivation profiles and PPARγ binding affinity. Applicability domain analysis carried out for PPARγ binding affinity revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.