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Influence of structural factors on the enhanced activity of moxifloxacin: a fluorescence and EPR spectroscopic study

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Abstract

Partition coefficients of moxifloxacin in liposomes of dimyristoyl-L-α-phosphatidylcholine or dimyristoyl-L-α-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.

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Acknowledgements

Partial financial support for this work was provided by “Fundação para a Ciência e Tecnologia” (FCT, Lisboa) through Project POCI/SAU-FCF/56003/2004. P.N. thanks FCT for a fellowship.

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Authors and Affiliations

  1. Faculdade de Ciências, Departamento de Química, REQUIMTE, 4169-007, Porto, Portugal

    Patrícia Neves, Baltazar de Castro & Paula Gameiro

  2. Instituto de Ciências Biomédicas Abel Salazar, REQUIMTE, 4099-003, Porto, Portugal

    Andreia Leite & Maria Rangel

Authors
  1. Patrícia Neves
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  2. Andreia Leite
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  3. Maria Rangel
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  4. Baltazar de Castro
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  5. Paula Gameiro
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Correspondence to Paula Gameiro.

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Neves, P., Leite, A., Rangel, M. et al. Influence of structural factors on the enhanced activity of moxifloxacin: a fluorescence and EPR spectroscopic study. Anal Bioanal Chem 387, 1543–1552 (2007). https://doi.org/10.1007/s00216-006-1009-x

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  • DOI: https://doi.org/10.1007/s00216-006-1009-x

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