3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors

The three-dimensional quantitative structure–activity relationships of 57 2-[(aminopropyl)amino]-4(1H)-quinolinone analogues as Staphylococcus aureus methionyl-tRNA synthetase (MetRS) inhibitors with excellent antibacterial profile were investigated and docking studies were performed. The CoMFA analysis provided a model with a q² value of 0.579 and an r² value of 0.970, in which the good correlation between the MetRS inhibitory activities (IC₅₀) and the steric and electrostatic molecular fields around the analogues was examined. Two inhibitors (1 and 17) were docked into the binding pocket of Escherichia coli MetRS imported from the X-ray crystal structure of the MetRS-methionine complex, and the details of their interaction with the amino acids of the active site are discussed.