3D-QSAR, design, docking and in silico ADME studies of indole-glyoxylamides and indolyl oxoacetamides as potential pancreatic lipase inhibitors

Abstract

The versatility of indole heterocyclic led to the understanding of their structural requirements to develop new potential derivatives. The indole derivatives estimated to be active against pancreatic lipase have been chosen to develop 3D-QSAR field and atom-based models, validated using the Schrodinger suite. Designing of new agents through QSAR based predictions and performing docking on these compounds helped in defining the binding pattern and pharmacophoric features like π–π stacking interactions, hydrogen bonding, and π-cation interactions with the amino acid residues. The protein-ligand complex displayed good binding energies. In silico ADMET properties have been generated using the Quick-prop module of the Schrodinger suite. The 3D-QSAR model is found to be statistically significant and evaluated using various parameters like R², R²CV, stability, F-value, P-value, RMSE, Q², and Pearson-r by PLS factor of 4. The field fractions and contour maps along with their visualizations have helped in inferring the essential nature and type of substituent that should be incorporated for a compound to display potent pancreatic lipase inhibitory activity. These deductions and evaluations of the synthesized compounds through the generation of models could be further utilized for designing new molecules rationally.