Identifications of good and bad structural fragments of hydrazone/2,5-disubstituted-1,3,4-oxadiazole hybrids with correlation intensity index and consensus modelling using Monte Carlo based QSAR studies, their molecular docking and ADME analysis

Abstract

ABSTRACT The application of QSAR along with other in silico tools like molecular docking, and molecular dynamics provide a lot of promise for finding new treatments for life-threatening diseases like Type 2 diabetes mellitus (T2DM). The present study is an attempt to develop Monte Carlo algorithm-based QSAR models using freely available CORAL software. The experimental data on the α-amylase inhibition by a series of benzothiazole-linked hydrazone/2,5-disubstituted-1,3,4-oxadiazole hybrids were selected as endpoint for the model generation. Initially, a total of eight QSAR models were built using correlation intensity index (CII) as a criterion of predictive potential. The model developed from split 6 using CII was the most reliable because of the highest numerical value of the determination coefficient of the validation set (r 2 VAL = 0.8739). The important structural fragments responsible for altering the endpoint were also extracted from the best-built model. With the goal of improved prediction quality and lower prediction errors, the validated models were used to build consensus models. Molecular docking was used to know the binding mode and pose of the selected derivatives. Further, to get insight into their metabolism by living beings, ADME studies were investigated using internet freeware, SwissADME.