Abstract

Introduction: The High-density lipoprotein (HDL) receptor, Scavenger receptor class B, type I (SRBI) plays a crucial role in lipoprotein metabolism, cholesterol homeostasis, and atherosclerosis. In the present study, a quantitative structure-activity relationship study (QSAR) investigation was conducted on a data set of 31 novel indolinyl thiazole-based inhibitors of SR-BI mediated lipid uptake.

Methods: To build the QSAR model, Multiple linear regression analysis (MLR), partial least square analysis (PLS), and neural analysis (NN) were performed which were further evaluated internally as well as externally for the prediction of activity. The best QSAR model for MLR was selected with a correlation coefficient (r2) of 0.937, cross-validation r2cv of 0.908, and a standard error (S) value of 0.253. For PLS, r2 was 0.937 and for FFNN r2 was 0.961 (for the training set). This was further evaluated externally by a test set having r2 values 0.870 (MLR), 0.863(PLS), and 0.933(neural network) analysis.

Results: The final model comprised hydrophobic parameters (Lipole Z component) and steric parameters (molar refractivity and K alpha2 index).

Conclusion: All these descriptors generated comparable results which prove that the model generated is sound and has good predictability.