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PAF receptor and “cache-oreilles” effect. Simple PAF antagonists

  • PAF Receptor and Antagonists
  • Published:
Lipids

Abstract

Nine simple and structurally flexible PAF antagonists were synthesized and their inhibitory effects on PAF induced platelet aggregation were measured. Compounds with PAF antagonistic activity exhibited a negative electrostatic potential generated by two trimethoxyphenyl groups (isocontour at −10 Kcal/mole) at various distances between the negative clouds. The optimal distance between the atoms generating the “cache-oreilles” system for exhibiting potent PAF antagonistic activity is estimated to be 11–13 Å. In the flexible molecules studied, the dispersion of the electronic distribution is not necessarily favorable for anti-PAF activity. The data support the simple bipolarized model for the PAF receptor that has been proposed by the authors.

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Abbreviations

CNDO:

complete neglect of differential overlap

3-D:

three dimensional (electrostatic potential map)

DMF:

dimethylformamide

HMDS:

hexamethyldisiloxane

IC50 :

50% inhibition

IR:

infrared spectroscopy

MM2:

molecular mechanics version 2

MMP2:

molecular mechanics π systems version 2

MNDO:

modified neglect of differential overlap

NMR:

nuclear magnetic resonance

PAF:

platelet activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine

PRP:

platelet-rich plasma

TLC:

thin-layer chromatography

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Author information

Authors and Affiliations

  1. Centre d'Ingéniérie des Protéines, Institut de Chimie, Liège-Sart-Tilman, Belgium

    J. Lamotte-Brasseur & G. Dive

  2. Institut Henri Beaufour, Le Plessis Robinson, France

    D. Hosford & P. Braquet

  3. Laboratoire de Pharmacochimie Moléculaire, Université Paris 7, 2, Place Jussieu, 75251, Paris Cedex 05, France

    F. Heymans, A. Lamouri, J. P. Batt, C. Redeuilh & J. J. Godfroid

Authors
  1. J. Lamotte-Brasseur
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  2. F. Heymans
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  3. G. Dive
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  4. A. Lamouri
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  5. J. P. Batt
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  6. C. Redeuilh
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  7. D. Hosford
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  8. P. Braquet
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  9. J. J. Godfroid
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Cite this article

Lamotte-Brasseur, J., Heymans, F., Dive, G. et al. PAF receptor and “cache-oreilles” effect. Simple PAF antagonists. Lipids 26, 1167–1171 (1991). https://doi.org/10.1007/BF02536524

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  • DOI: https://doi.org/10.1007/BF02536524

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