Abstract
Several 3-formylquinolone derivatives (8a-c) were synthesized to assay the antibacterial activity both in vitro and in vivo. In vitro, all of the compounds 8a-c showed lower activity than that of the corresponding 3-carboxyl compounds 1a-c, and in vivo, they showed higher activity than that of compounds 1a-c. After oral administration of 3-formyl compounds 8a-c to mice, the compounds were rapidly metabolized into 3-carboxyl compounds 1a-c. In particular, the 3-formyl derivative (8a) of norfloxacin (NFLX, 1a) gave a 2-fold higher serum level than that of NFLX and functioned as a prodrug of NFLX.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Biological Availability
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Ciprofloxacin / analogs & derivatives*
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Ciprofloxacin / chemical synthesis
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Ciprofloxacin / pharmacology
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Ciprofloxacin / therapeutic use
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Escherichia coli Infections / drug therapy
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Fluoroquinolones*
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Gram-Negative Bacteria / drug effects
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Gram-Positive Bacteria / drug effects
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Indicators and Reagents
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Mice
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Mice, Inbred Strains
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Microbial Sensitivity Tests
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Norfloxacin / analogs & derivatives*
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Norfloxacin / chemical synthesis
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Norfloxacin / pharmacology
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Norfloxacin / therapeutic use
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Pefloxacin* / analogs & derivatives*
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Pharmaceutical Preparations / chemical synthesis*
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Prodrugs / chemical synthesis*
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Fluoroquinolones
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Indicators and Reagents
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Pharmaceutical Preparations
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Prodrugs
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1-ethyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline
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1-cyclopropyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline
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1-ethyl-6-fluoro-3-formyl-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline
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Pefloxacin
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Ciprofloxacin
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Norfloxacin