title: Synthesis and antibacterial evaluation of novel 4″-glycyl linked quinolyl-azithromycins with potent activity against macrolide-resistant pathogens.
abstract: A new azithromycin-based series of antibacterial macrolones is reported, which features the use of a 4″-ester linked glycin for tethering the quinolone side chain to the macrolide scaffold. Among the analogs prepared, compounds 9e and 22f with a quinolon-6-yl moiety were found to have potent and well-balanced activity against clinically important respiratory tract pathogens, including erythromycin-susceptible and MLSB resistant strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. In addition, potential lead compounds 9e and 22f demonstrated outstanding levels of activity against Moraxella catarrhalis and inducibly MLSB resistant Staphylococcus aureus. The best member of this series 22f rivals or exceeds, in potency, some of the most active ketolide antibacterial agents known today, such as telithromycin and cethromycin.
authors: PLIVA Research Institute, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia. Electronic address: dpavlovic@hotmail.fr.
authors: Dražen
authors: D
authors: Pavlović
authors: PLIVA Research Institute, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors: Stjepan
authors: S
authors: Mutak
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017963:Azithromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D017963:Azithromycin
keywords: C-4″-substituted azithromycins; Macrolide antibiotics; Macrolide resistance; Quinolones