Anti-thrombotic activity of water-soluble calix[n] arenes

被引：37

作者：

De Silva, E ^{[1
]}

Ficheux, D ^{[1
]}

Coleman, AW ^{[1
]}

机构：

[1] CNRS, Inst Biol & Chim Prot, UMR 5086, F-69367 Lyon, France

来源：

JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY | 2005年 / 52卷 / 3-4期

关键词：

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

D O I：

10.1007/s10847-004-6715-4

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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-octasulfonatocalix[ 8] arene ( C8SMA) and 5,11,17,23,29,35-hexa-sulfonato-calix[ 6] arene (C6S) produce activation of HCII at 500 lMcomparable to that induced by DS at 100 mu M. 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.

引用

页码：201 / 206

页数：6

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