title: Synthesis and antibacterial evaluation of novel clarithromycin derivatives with C-4″ elongated arylalkyl groups against macrolide-resistant strains.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China. mashutao@sdu.edu.cn
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Jiao
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Ju
authors.forename: Manjie
authors.initials: M
authors.lastname: Zheng
authors.forename: Ruixin
authors.initials: R
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Xuecui
authors.initials: X
authors.lastname: Shen
authors.forename: Chenchen
authors.initials: C
authors.lastname: Ma
authors.forename: Ya
authors.initials: Y
authors.lastname: Meng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yunkun
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
authors.forename: Wenping
authors.initials: W
authors.lastname: Cui
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017291:Clarithromycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013211:Staphylococcus aureus / Q000187:drug effects*; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017291:Clarithromycin