title: Synthesis and antibacterial activity of novel 4''-O-carbamoyl erythromycin-A derivatives.
abstract: Novel 4''-O-carbamoyl erythromycin-A derivatives were designed, synthesized, and evaluated for their in-vitro antibacterial activities. All of the 4''-O-carbamoyl derivatives showed excellent activity against erythromycin-susceptible Staphylococcus aureus ATCC25923, Streptococcus pyogenes, and Streptococcus pneumoniae ATCC49619. Most of the 4''-O-arylalkylcarbamoyl derivatives displayed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene or the erm and mef genes. In particular, the 4''-O-arylalkyl derivatives 4c-4e and 4g were found to possess the most potent activity against all the tested erythromycin-susceptible strains, which were comparable to those of erythromycin, clarithromycin, or azithromycin. 4''-O-Arylalkyl derivatives 4e and 4g were the most effective against erythromycin-resistant S. pneumoniae encoded by the mef gene (0.25 and 0.25 microg/mL). 4''-O-Arylalkyl derivatives 4a and 4b exhibited significantly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. In contrast, the 4''-O-alkylcarbamoyl derivatives hardly showed improved activity against all the tested erythromycin-resistant strains.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, P R China.
authors.forename: Yunkun
authors.initials: Y
authors.lastname: Qi
authors.forename: Bo
authors.initials: B
authors.lastname: Jiao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
authors.forename: Wenping
authors.initials: W
authors.lastname: Cui
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin