Quantum mechanical, virtual screening, molecular docking, molecular dynamics, ADME and antimicrobial activity studies...

In this study, a new series of indole-5-carbaldehyde hydrazone derivative compounds were designed, synthesized, and their antimicrobial activities were determined by the microdilution method, and the in vitro cytotoxic effects on Beas-2b cell lines were investigated by MTT assay. When the activity results were examined, 5i12 showed promising activity against E. faecalis with MIC: 2 µg/mL compared to ampicillin, gentamicin, and vancomycin, although the antimicrobial activities of the indole derivatives were generally weaker than those of the standard drugs. Compounds showed no cytotoxic activity on the A549, MCF-7, and Beas-2b cell lines. Molecular docking studies were performed on 15 different proteins to understand the mechanism of 5i12's good antimicrobial action against E. faecalis, and it was concluded that the compounds interacted with FabH, not enough other protein structures. Molecular dynamics simulations were performed to investigate the protein-ligand stability of the most active compound against E. faecalis. The RMSD value of 5i12 varied between 0.02 and 0.16 nm during the MD simulation. The apoprotein peaked at 0.55 nm at the beginning of the simulation and stabilized below 0.5 nm. The theoretical ADME profiles of all compounds were calculated and found to comply with Lipinski and other limiting rules. In addition, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis for 5i12 were calculated using the 6-311 G (d,p) base set and DFT/B3LYP theory, and the results were visualized. Communicated by Ramaswamy H. Sarma.