title: Novel C-4'' modified azithromycin analogs with remarkably enhanced activity against erythromycin-resistant Streptococcus pneumoniae: the synthesis and antimicrobial evaluation.
abstract: Three novel structural series of C-4'' modified azithromycin analogs with two amide groups, which were connected by different alkyl linkage, were designed, prepared and evaluated for their in vitro antibacterial activity against seven phenotypes of respiratory pathogens. Among them, 7d, 8j and 9j, as representatives of corresponding series, exhibited remarkably improved activity against erythromycin-resistant Streptococcus pneumoniae expressing the erm gene, the mef gene, and the erm and mef genes. In addition, 7a-c, 7f-h, 7j, 8d, 8g, 8i, 9a-b and 9i displayed favorable efficacy against erythromycin-resistant S. pneumoniae A22072 expressing the mef gene.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Rongmei
authors.initials: R
authors.lastname: Wang
authors.forename: Jichao
authors.initials: J
authors.lastname: Cao
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Jida
authors.initials: J
authors.lastname: Wang
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017963:Azithromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D004917:Erythromycin; D017963:Azithromycin