The imidazolidone analogs as phospholipase D1 inhibitors: Analysis of the three-dimensional quantitative structure-activity relationship

Abstract

Phospholipase D1 (PLD1) is one of the important enzymes in cell proliferation, apoptosis, and tumor progression. Quantitative structure-activity relationship (QSAR) analysis of PLD1 inhibitors was performed to obtain a good predictive model for providing structural rationale for the activity of inhibitors. The 3D-QSAR analysis was carried out on 31 imidazolidonebased analogs of PLD1 inhibitors in the training set. The molecular field analysis (MFA) with G/PLS method was used to generate a statistically significant 3D-QSAR model (r 2 = 0.930) based on molecular field generated by electrostatic and steric probes. The QSAR model was validated using leave-one-out cross-validation, bootstrapping and randomization methods, and finally with an external test set comprising nine inhibitors. The analysis of the best MFA model provided insights into possible modifications for the rational design of imidazolidone analogs as PLD1 inhibitors for better activity. © Springer Science+Business Media, LLC 2011.