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.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / pharmacology
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Clarithromycin / analogs & derivatives
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Clarithromycin / chemical synthesis*
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Clarithromycin / pharmacology
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Drug Resistance, Bacterial / drug effects
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Drug Resistance, Bacterial / genetics
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Erythromycin / pharmacology
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Gene Expression
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Hydrazines / chemistry*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Methyltransferases / genetics
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Methyltransferases / metabolism
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / genetics
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Staphylococcus aureus / growth & development
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Streptococcus pneumoniae / drug effects*
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Streptococcus pneumoniae / genetics
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Streptococcus pneumoniae / growth & development
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Benzimidazoles
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Hydrazines
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MefA protein, Streptococcus
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Membrane Proteins
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Erythromycin
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Methyltransferases
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ErmA protein, Bacteria
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Clarithromycin