EFFECT OF MAGNESIUM COMPLEXATION BY FLUOROQUINOLONES ON THEIR ANTIBACTERIAL PROPERTIES

By using infrared and F-19 nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium f or six fluoroquinolones. It was proven that magnesium is situated betw een the ketone and the carboxylate groups. We determined the binding c onstants for the 1:1 Mg2+-drug complex in solution. Sparfloxacin and p efloxacin, with affinity constants (K alpha) of (10.1 +/- 0.6) x 10(2) M(-1) and (21 +/- 1) x 10(2) M(-1), respectively, were the least and the most bound, respectively. The trend of the affinities of the assay ed fluoroquinolones for magnesium was correlated with their antimicrob ial activities against four bacteria and with their accumulation by th ese bacteria. The reference strain, Escherichia coli KL16, and two res istant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium.