In silico Characterization, ADMET prediction and Molecular Docking studies of few 2/3 carboxylate-4/5/6-monosubstitued indole derivatives as potential GSK-3β inhibitors

Abstract

Diabetes Mellitus is a leading cause of high mortality rate in the world. Recently, GSK-3β inhibitors showed promising results to treat Diabetes mellitus and several such molecules are in clinical trials. Ethyl 2/3-carboxylate-4/5/6-monosubstituted-1H-indole derivatives were designed with the aim to search new lead molecules. The molecular structures were drawn in ChemBiodraw Ultra© and molecular docking studies were performed by using Schrödinger and AutoDock 1.5.6 software. Few in silico properties such as Log P and toxicity profile were predicted online using SwissADME and PreADMET respectively. Amongst all the designed molecules, few derivatives showed maximum binding affinity in LBD of 6V6L protein. The lipophilic character of the molecules was predicted through their individual Log P Values; molecules with better binding affinities in LBD displayed Log P values of 2.25-3.13. Additionally, some of the designed molecules were subjected to PreADMET for predicting their safety and few were predicted to induce toxic reaction were as others were predicted to be safe in the models that were selected for prediction. Ethyl 2/3-carboxylate-4/5/6-monosubstituted-1H-indole derivative were designed resulting in new molecules with high binding affinities, also few of these molecules were predicted to be non-carcinogenic with low Log P values.