Use of Simplified Molecular Input Line Entry System and molecular graph based descriptors in prediction and design of pancreatic lipase inhibitors.

Abstract

The inhibition of pancreatic lipase (PL) enzyme is the most explored strategy for the treatment of obesity. The present study describes the development of quantitative structure-activity relationship (QSAR) models for a diverse set of 293 PL inhibitors by means of the Monte Carlo optimization technique. Methodology & results: The hybrid optimal descriptors were used to build QSAR models with three subsets of three splits. The developed QSAR models were further validated with corresponding external sets. The best QSAR model has the following statistical particulars: R2=0.752, Q LOO 2 = 0 . 736 for the test set and R2=0.768, Q F 1 2 = 0 . 628 , Q F 2 2 = 0 . 621 for the validation set. The developed QSAR models were robust, stable and predictive and led to the design of novel PL inhibitors.