Synthesis and Antibacterial Evaluation of a Series of 1112-Cyclic Carbonate Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives

摘要

A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against seven kinds of susceptible strains. In particular, compound >G1 exhibited the most potent activity against methicillin-resistant Streptococcus pneumoniae 943 (MIC: 1 μg/mL), Staphylococcus pneumoniae 746 (MIC: 2 μg/mL), Streptococcus pyogenes 447 (MIC: 8 μg/mL), and Escherichia coli 236 (MIC: 32 μg/mL), which were two-, four-, four-, four-, and eight-fold stronger activity than azithromycin, respectively. Additionally, compound >G2 exhibited improved activity against methicillin-resistant Staphylococcus aureus MRSA-1 (MIC: 8 μg/mL), Streptococcus pneumoniae 943 (MIC: 2 μg/mL), Staphylococcus pneumoniae 746 (MIC: 2 μg/mL), and Escherichia coli 236 (MIC: 32 μg/mL), which were two-, two-, four-, and eight-fold better activity than azithromycin, respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound >G6 presented the most excellent activity (MIC: 4 μg/mL), showing four-fold higher activity than azithromycin (MIC: 16 μg/mL) and erythromycin (MIC: 16 μg/mL). However, compared with other compounds, compounds >G7 and >G8 with the disaccharide side chain were observed the lower activity against seven strains.