Synthesis and antibacterial activity of novel 11,12-cyclic carbonate azithromycin 4''-O-carbamate derivatives.
A series of novel 11,12-cyclic carbonate azithromycin 4''-O-carbamate derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 7b and 7d were the most effective (0.5 and 0.5 microg ml(-1)) against two strains of erythromycin-resistant Streptococcus pneumoniae whose resistance was encoded by the erm gene and the erm and mef genes, respectively. Compounds 7a, 7e and 7g showed significantly potent activity against erythromycin-susceptible strains such as Staphylococcus aureus and S. pyogenes. These results suggest that the introduction of the prolonged arylalkylcarbamoyl group to the C-4'' position can dramatically enhance the activity against erythromycin-resistant bacteria encoded by the erm gene or the erm and mef genes.
Ma
Chenchen
C
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
Liu
Zhaopeng
Z
Song
Hualong
H
Jiang
Rentao
R
He
Fawen
F
Ma
Shutao
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017963:Azithromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology; D002254:Carbonates / Q000138:chemical synthesis / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D013297:Streptococcus pyogenes / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002219:Carbamates; D002254:Carbonates; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D004917:Erythromycin; D017963:Azithromycin; C111078:ErmTR protein, bacteria; D008780:Methyltransferases