Novel Glycoconjugate of 8-Fluoro Norfloxacin Derivatives as Gentamicin-resistant Staphylococcus aureus Inhibitors: Synthesis and Molecular Modelling Studies.

ABSTRACT

Antibiotic resistance has been the subject of interest in clinical practice due to high prevalence of antibiotic-resistant pathogenic organisms. In view of the prevalence of lesser resistance in antibiotics belonging to aminoglycoside class of compounds viz. Food and Drug Administration-approved gentamicin for the treatment of Staphylococcus infections, which also has instances of resistance in the clinical isolates of Staphylococcus aureus, a series of novel glycoconjugates of 8-fluoro norfloxacin analogues with high regio-selectivity by employing copper (I)-catalyzed 1, 3-dipolar cycloaddition of 1-O-propargyl monosaccharides has been synthesized and evaluated for the antibacterial activity against gentamicin resistance Staphylococcus aureus. Among these compounds, the compound 10g showed better antibacterial activity (MIC = 3.12 µg/ml) than gentamicin (Escherichia coli (12.5 µg/ml), Staphylococcus aureus (6.25 µg/ml) and Klebsiella pneumonia (6.25 µg/ml), including gentamicin resistant (>50 µg/ml) strain in vitro). The docking studies suggest DNA gyrase of Staphylococcus aureus as a probable target for the antibacterial action of compound 10g.