6-hydroxy derivative as new desfluoroquinolone (DFQ): synthesis and DNA-binding study.
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.
Tabarrini
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Istituto di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Italy.
Sissi
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Fravolini
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A
Palumbo
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M
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004269:DNA, Bacterial / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines; D059005:Topoisomerase II Inhibitors
C421503:1-cyclopropyl-6-hydroxy-8-methyl-4-oxo-7-(1,2,3,4-tetrahydro-2-isoquinolyl)-1,4-dihydroquinoline-3-carboxylic acid; D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D015363:Quinolones; D044005:Tetrahydroisoquinolines; D059005:Topoisomerase II Inhibitors; D005461:Fluorine; D008274:Magnesium