title: Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cong
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Siti
authors.initials: S
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jichao
authors.initials: J
authors.lastname: Cao
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D017291:Clarithromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology; D015870:Gene Expression; D006834:Hydrazines / Q000737:chemistry*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001562:Benzimidazoles; D006834:Hydrazines; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D004917:Erythromycin; D008780:Methyltransferases; C431709:ErmA protein, Bacteria; D017291:Clarithromycin