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 antibacter ial activity unambiguously shows that the hydroxyl group is a good substitu te 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, displa ying the highest IC50 value observed for all the C-6 substituted analogues. This behaviour could be explained on the basis of its DNA binding properti es.