Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives

Novel 4″-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These benzimidazolyl derivatives exhibited excellent activity against erythromycin-susceptible strains better than the references, and some of them showed greatly improved activity against erythromycin-resistant strains. Compounds 16 and 17, which have the terminal 2-(4-methylphenyl)benzimidazolyl and 2-(2-methoxyphenyl)benzimidazolyl groups on the C-4″ bishydrazide side chains, were the most active against erythromycin-resistant Staphylococcus pneumoniae expressing the erm gene and the mef gene. In addition, compound 17 exhibited the highest activity against erythromycin-susceptible S. pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923 as well. It is worth noting that the 4″-O-(2-aryl)benzimidazolyl derivatives show higher activity against erythromycin-susceptible and erythromycin-resistant strains than the 4″-O-(2-alkyl)benzimidazolyl derivatives.

Novel 4″-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Compound 17 showed the highest activity against the erythromycin-susceptible and the erythromycin-resistant strains, much better than the references.Figure optionsDownload as PowerPoint slideHighlights
► Novel 4″-O-benzimidazolyl clarithromycin derivatives were synthesized and evaluated.
► The derivatives showed excellent activity against erythromycin-susceptible strains.
► Some of them showed greatly improved activity against erythromycin-resistant strains.
► 4″-O-(2-aryl)benzimidazolyl derivatives had higher activity than other derivatives.
► The other derivatives are the 4″-O-(2-alkyl)benzimidazolyl derivatives of CAM.