title: 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.
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Azad
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Shome S
authors.initials: SS
authors.lastname: Bhunia
authors.affiliation: Fermentation Technology Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Krishna
authors.affiliation: Fermentation Technology Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D024881:Drug Resistance, Bacterial; D005839:Gentamicins; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009643:Norfloxacin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000254:growth & development*
chemical_list: D005839:Gentamicins; D006001:Glycoconjugates; D009643:Norfloxacin
keywords: drug discovery; molecular modeling; molecular recognition; therapeutic target