Synthesis, spectroscopic characterization, DFT, molecular docking and in vitro antibacterial potential of novel quinoline derivatives

Abstract In this work, three new quinolone derivatives were prepared by alkylation of 2-oxo-1,2-dihydroquinoline-4-carboxylic acid with ethyl 2-bromoacetate. The synthesized compounds 2-4 were characterized by using FT-IR, 1H NMR, 13C NMR and mass spectrometry. Crystal structure of 4 was determined by single crystal X-ray diffraction. The optimized structures of 2-4 in gas phase, 1H and 13C NMR chemical shifts, molecular electrostatic potential (MEP), frontier orbitals and non-linear properties (NLO) have been investigated by using the B3LYP/6-311++G(d,p) method. All compounds were evaluated in vitro for their antibacterial activities against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC4157, Streptococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 bacterial strains. The tested compounds exhibited a good to moderate antibacterial activity with MIC values between 6.25 and 50 μg/mL, when compared to references Ampicillin and Chloramphenicol. Among the three compounds, compound 4 showed the most potent antibacterial activity against S. aureus with MIC value of 6.25 μg/mL. In addition, molecular docking studies of compounds 2-4 were performed within the active site of PDB: 2ZCQ protein to analyze the binding interactions responsible for their activities.