Abstract
A new 6-desfluoroquinolone derivative, characterized by the presence of a 6-hydroxyl group instead of the usual fluorine atom at the C-6 position, was synthesized with the aim to better understand the mechanistic role of the C-6 substituent in the quinolone/DNA/DNA-gyrase interaction. The antibacterial activity unambiguously shows that the hydroxyl group is a good substitute for the C-6 fluorine atom, especially against Gram-positive bacteria. On the contrary, it is a very weak inhibitor of the target DNA gyrase, displaying the highest IC50 value observed for all the C-6 substituted analogues. This behaviour could be explained on the basis of its DNA binding properties.
MeSH terms
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / metabolism
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Anti-Infective Agents / pharmacology
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DNA, Bacterial / metabolism
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DNA, Single-Stranded / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Fluorine / chemistry
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Gram-Negative Bacteria / drug effects
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Gram-Positive Bacteria / drug effects
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Magnesium / metabolism
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Microbial Sensitivity Tests
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Molecular Structure
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Quinolones / chemical synthesis*
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Quinolones / chemistry
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Quinolones / metabolism
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Quinolones / pharmacology
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Structure-Activity Relationship
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Tetrahydroisoquinolines*
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Topoisomerase II Inhibitors*
Substances
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1-cyclopropyl-6-hydroxy-8-methyl-4-oxo-7-(1,2,3,4-tetrahydro-2-isoquinolyl)-1,4-dihydroquinoline-3-carboxylic acid
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Anti-Infective Agents
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DNA, Bacterial
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DNA, Single-Stranded
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Enzyme Inhibitors
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Quinolones
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Tetrahydroisoquinolines
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Topoisomerase II Inhibitors
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Fluorine
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Magnesium