Mg(2+)-mediated binding of 6-substituted quinolones to DNA: relevance to biological activity

Bioorg Med Chem. 1998 Sep;6(9):1555-61. doi: 10.1016/s0968-0896(98)00086-8.


The interaction of a number of novel 6-substituted quinolone derivatives with DNA in the presence/absence of magnesium ions has been investigated by fluorometric techniques. The drug-single-stranded nucleic acid interaction is invariantly mediated by the metal ion. In all cases optimal complex formation is found at physiological Mg2+ concentration. From titrations at different [Mg2+] the binding constant for the ternary drug-DNA-Mg2+ complex (KT) has been evaluated. Interestingly, a good relationship is found between KT and gyrase poisoning activity of the test quinolones (IC50), which confirms that DNA-affinity of the quinolone, modulated by Mg2+, plays an important role in poisoning the cleavable gyrase-DNA complex and, consequently, in eliciting antibacterial activity in this family of drugs. The results obtained with different 6-substituted compounds supports the idea that position 6 of the drug, besides playing a pharmacokinetic role, is involved in recognition of the enzyme pocket. Our data do not support a mechanism of action based upon quinolone intercalation into B-DNA.

MeSH terms

  • Binding Sites
  • DNA, Single-Stranded / metabolism*
  • Fluorometry
  • Magnesium / metabolism*
  • Quinolones / metabolism*


  • DNA, Single-Stranded
  • Quinolones
  • Magnesium