Influence of structural factors on the enhanced activity of moxifloxacin: a fluorescence and EPR spectroscopic study.
Partition coefficients of moxifloxacin in liposomes of dimyristoyl-L-alpha-phosphatidylcholine or dimyristoyl-L-alpha-phosphatidylglycerol and water were determined by spectrophotometry and fluorimetry. The K (p) values obtained were larger than those reported for most of the other fluoroquinolones, a consequence of the structural changes observed in the molecule of moxifloxacin, which in turn change its acid/base properties. Introduction of a methoxy group at position 8 and a diazabicyclonyl ring at position 7 in the basic fluoroquinolone structure alters the charge distribution at the physiological pH of 7.4, and these changes seem to be responsible for its improved antibacterial potency and broader spectrum of activity. Location studies have also been performed using fluorescence and electron paramagnetic resonance (EPR) spectroscopies. The results show that moxifloxacin must be located near the phospholipid headgroups, similar to other fluoroquinolones, but contributions from a hydrophobic component were also detected. These results suggest that the enhanced activity of this drug may be related to a more facilitated entrance into the bacterial cell, perhaps including a mediator step involving electrostatic interaction with a hydrophobic component; this step then controls the extent or orientation of insertion and improves the electrostatic interaction.
Neves
Patrícia
P
Faculdade de Ciências, Departamento de Química, REQUIMTE, 4169-007 Porto, Portugal.
Leite
Andreia
A
Rangel
Maria
M
de Castro
Baltazar
B
Gameiro
Paula
P
D016880:Anisotropy; D001372:Aza Compounds / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D024841:Fluoroquinolones / Q000737:chemistry; D015394:Molecular Structure; D000077266:Moxifloxacin; D011804:Quinolines / Q000737:chemistry*; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013696:Temperature
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin