Docking Studies on Novel Analogues of 8-Chloro-Quinolones against Staphylococcus aureus

Abstract

Molecular docking studies have been carried out for a better understanding of the drug- receptor interactions. All the synthesized compounds have been subjected to molecular docking against targets that have been chosen based on the specific mechanism of action of the quinolones used in the antibacterial activity screening. A study of the characteristics and molecular properties of the small molecule known as ligand has been realized. In the first stage of the study, the 2D and 3D structures have been generated. The most stable conformer for each structure was obtained by geometry optimization and energy minimization. A series of topological, conformational characteristics and QSAR properties, important to assess the flexibility and the ability of the studied conformer to bind to the protein receptor, were deter- mined and analyzed. These properties were discussed in order to assess the flexibility and the binding ability of studied conformers to bind to the receptor protein. The docking stud - ies have been carried out. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolones in the active site of the protein receptor. morpholine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the HOMO of 7-pyrrolidinyl-8-unsubstituted-quinolone, FPQ 35 electron density is localized on pyrrolidine heterocyclic, on aromatic ring and on 4-oxo group. For the HOMO of 7-pyrro-lidinyl-8-chloro-quinolone, FPQ 36 electron density is localized on pyrrolidine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the LUMO of 7-substituted-8-unsubstituted-quinolones, NF, PF, FPQ27, O 83, FPQ 24, FPQ 32, electron density of FPQ 25 and FPQ 35 is localized on 4-piridinona ring and on aromatic ring. For the LUMO of 7-substituted-8-chloro-quinolones, electron density of FPQ 50, FPQ 51, FPQ29, O 85, FPQ 30, FPQ 33, FPQ 28 and FPQ 36 is localized on 4-piridinona ring, on aromatic ring B and on chlorine atom. For the 6-cloroqinolones, the electron density is located in the same manner as the corresponding fluoroquinolones.