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Anti-thrombotic Activity of Water-soluble Calix[n]arenes

  • E. Da. Silva
  • D. Ficheux
  • A. W. Coleman
Article

Abstract

The parent p-sulfonato-calix[n]arenes and six O-monosubstituted derivatives were investigated in vitro for anticoagulant activity. Different concentrations of calixarenes were tested, showing that the compound 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) has a significantly strong prolongation on the activated partial thromboplastin time (APTT) and on the thrombin time (TT) than the other calixarenes. Secondly, investigation of whether the anticoagulant behaviour was via interaction with antithrombin or Heparin Cofactor II was determined. Thrombin inhibition mediated by antithrombin (AT) and Heparin Cofactor II (HCII) activation was investigated in comparison to the biological activators, Heparin (Hep) and Dermatan sulfate (DS). The results show that the 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) and 5,11,17,23,29,35-hexa-sulfonato-calix[6]arene (C6S) produce activation of HCII at 500 μM comparable to that induced by DS at 100 μM. However, activation of AT by all of the investigated calixarenes is between 10 and 50 times lower than that observed in the presence of heparin. The mechanism of the anticoagulant effect of these calixarenes is as activators of HCII and not as activators of AT.

Keywords

anticoagulant antithrombin coagulation time heparin cofactor para-sulfonato-calix[n]arenes 

Abbreviations

APTT

activated partial thromboplastin time

AT

antithrombin

DS

dermatan sulfate

GAG

glycosaminoglycan

HCII

Heparin Cofactor II

TT

thrombin time

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Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Institut de Biologie et Chimie des ProtéinesCNRS-UMR 5086LyonFrance

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