Synthesis and antibacterial evaluation of novel clarithromycin derivatives with C-4″ elongated arylalkyl groups against macrolide-resistant strains

Novel clarithromycin derivatives with C-4″ elongated arylalkyl groups were designed, synthesized and evaluated to probe the effect of different lengths of their C-4″ side chains on the activity against resistant bacterial strains. These derivatives had excellent activity against erythromycin-susceptible Streptococcus pneumoniae, Streptococcus aureus or Streptococcus pyogenes and some of them exhibited greatly improved activity against erythromycin-resistant strains. Compounds 18 and 16, which had the C-4″ elongated arylalkyl groups with eight atoms from the 4″-oxygen atom to the terminal benzene ring, were the most effective against S. pneumoniae expressing the erm gene and the erm and mef genes. In contrast, the most potent compounds 3, 5, 9, 17 and 18 against S. pneumoniae expressing the mef gene had C-4″ elongated arylalkyl groups with three to eight atoms between the 4″-oxygen atom and the terminal aromatic ring.

33 novel clarithromycin derivatives with elongated C-4″ side chains were synthesized and evaluated to probe the effect of different lengths of their C-4″ side chains on activity against resistant bacterial strains.Figure optionsDownload as PowerPoint slideResearch highlights
► Novel clarithromycin derivatives with elongated C-42 side chains were synthesized.
► Their antibacterial activity was evaluated.
► The derivatives had excellent activity against erythromycin-susceptible strains.
► Some of them showed greatly improved activity against erythromycin-resistant strains.
► The lengths of their C-42 side chains affected activity against resistant bacteria.