Calix[4]resorcinarene derivatives bearing phosphonоacetomethoxy- and sulfonate groups at the upper rim of the macrocycle have been studied with respect to their effects on fibrin polymerization. Polymerization process was studied by atomic force microscopy and UV-vis spectroscopy. At concentration of 2.0·10 -6 M of the calix[4]resorcinarene the maximum rate of fibrin polymerization in the fibrinogen + thrombin reaction decreased by 98,6%, in case of the phosphonic derivative, and by 96,4%, in case of the sulfonate derivative. At this concentration, the molar ratio of the calix[4]resorcinarene to fibrinogen was 6,8 : 1. Further confirmation that the inhibitor was acting at the initial step of the polymerization was obtained by atomic-force microscopy. No evidence of large protofibrils but formation of microfibrillar matrix on the surface of mica, incubated in the reaction medium, has been shown. These experiments demonstrate that the studied calix[4]resorcinarene derivatives are potential inhibitors of fibrin polymerization and can be used for the design of a new class of antithrombotic agents.
фибриноген, фибрин, антитромботические агенты, каликс[4]резорцинарены, fibrinogen, fibrin, antithrombotic agents, calix[4]resorcinarene
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