In silico studies of 2-aryloxy-1,4- naphthoquinone derivatives as antibacterial agents against Escherichia coli using 3D-QSAR, ADMET properties, molecular docking, and molecular dynamics

Abstract

In this study, we investigated 30 derivatives of naphthoquinone using 3D-QSAR, drug-likeness, ADMET, molecular docking, and dynamics techniques in silico. The objective is carried out to elaborate the robust 3D-QSAR models using the CoMFA to discover new antibacterial agents against Escherichia coli. High predictive power has been demonstrated by the QSAR models based on their evaluations (Q² = 0.613, R² = 0.902, SEE = 0.063). Using the QSAR model predictions, new four molecular structures are designed. As a next step, we examined the four compounds' drug-likeness and ADMET predictions. Two compounds have excellent ADMET predictions and drug-likeness. Molecular docking was used to examine the bindings established between the newly designed molecule 1 and 2 with the protein. Based on the obtained results, the compound 2 exhibits high stability. To confirm this stability, we performed molecular dynamics during 100 ns under three different temperature conditions. High stability was confirmed by molecular dynamics simulations.