title: 3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors.
abstract: 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 q(2) value of 0.579 and an r(2) value of 0.970, in which the good correlation between the MetRS inhibitory activities (IC(50)) 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.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D008715:Methionine / Q000737:chemistry; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000201:enzymology
chemical_list: D015363:Quinolones; D008715:Methionine; D008718:Methionine-tRNA Ligase