NMR studies of interactions of new CB2 cannabinoid receptor ligands with cyclodextrins hosts. Correlation with micellar electrokinetic chromatography and reversed phase high performance liquid chromatography

  • Nathalie Azaroual
  • Jamal El Bakali
  • Delphine Le Broc
  • Carole Deghaye
  • Amaury Farce
  • Philippe Chavatte
  • Régis Millet
  • Claude Vaccher
  • Emmanuelle Lipka-Belloli
Original Article
  • 272 Downloads

Abstract

Three selective CB2 cannabinoid receptor ligands have recently been discovered to be promising anti-inflammatory agents but their low water solubility hinder their per os administration. The popularity of the cyclodextrins, from a pharmaceutical standpoint lies on their ability to interact with poorly water-soluble drugs and improve their solubility. Herein, three experimental approaches for calculating the stability constant of complexes between the selective CB2 ligands and either the β-CD or the HP-β-CD, were tested: nuclear magnetic resonance, micellar electrokinetic chromatography and high performance liquid chromatography in reversed phase. In NMR studies the calculated K values were relatively high and were between 1486 and 3571 M−1 with β-CD. With HP-β-CD they were between 1203 and 2650 M−1. Concerning the two others techniques the K values were found lower. In MECK studies with β-CD they were between 308 and 792 M−1 and with HP-β-CD between 124 and 764 M−1. Finally in RP-HPLC studies with β-CD, they were between 539 and 1144 M−1 and with HP-β-CD between 196 and 396 M−1. These calculated constants suggest that a complexation phenomenon occurs. A model for inclusion of one of the CB2 ligands in the β-CD was then proposed from molecular modeling studies.

Keywords

IBD 4-oxo-1 4-Dihydropyridine Solubility Formation constant Molecular modeling studies 

Notes

Acknowledgments

This work was financially supported by a grant from the Nord-Pas-de-Calais Regional Council and University of Lille 2. The 500 MHz NMR facilities were funded by the Région Nord-Pas de Calais (France), the Ministère de la Jeunesse, de l’Education Nationale et de la Recherche (MJENR) and the Fonds Européens de Développement Régional (FEDER).

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Nathalie Azaroual
    • 1
  • Jamal El Bakali
    • 1
  • Delphine Le Broc
    • 2
  • Carole Deghaye
    • 1
  • Amaury Farce
    • 1
  • Philippe Chavatte
    • 1
  • Régis Millet
    • 1
  • Claude Vaccher
    • 1
  • Emmanuelle Lipka-Belloli
    • 1
    • 3
  1. 1.UDSL, EA 4481Université Lille Nord de FranceLilleFrance
  2. 2.UDSL, EA 4483Université Lille Nord de FranceLilleFrance
  3. 3.Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et BiologiquesUniversité de Lille 2Lille CedexFrance

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