Supercooperativity in platelet aggregation: Substituted pyridyl isoxazoles, a new class of supercooperative platelet aggregation inhibitors

FEBS Letters

Shram, Stanislav I.¹  Varfolomeev, Sergey D.¹  Demina, Olga V.¹  Vrzheshch, Peter V.¹ 

[1] Department of Chemistry, Moscow State University, 119899 Moscow, Russian Federation

关键词: Platelet aggregation;    Inhibition;    Supercooperativity;    Substituted pyridyl isoxazole;    Tx;    thromboxane;    PTA2;    pinane thromboxane A2;    GP;    glycoprotein;    ADP;    adenosine diphosphate;    AMP;    adenosine monophosphate;    F;    cell response;    A;    inducer;    I;    inhibitor;    h;    Hill coefficient;    PRP;    platelet-rich plasma;    PPP;    platelet-poor plasma;    DMSO;    dimethylsulfoxide;   

DOI  :  10.1016/0014-5793(94)00845-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The phenomenon of supercooperativity in platelet aggregation is manifested by the occurence of clear-cut thresholds in dose—response relationships; in such cases the Hill coefficient has unusually high values. Approximation, by the Hill equation, of the relationship of the rate of arachidonate-induced platelet aggregation to the concentrations of either the inducer or inhibitors such as substituted pyridyl isoxazoles (synthesized by us), indomethacin, and pinane thromboxane A₂, demonstrated that the Hill coefficients ranged from 30 to 100. 3-(3-Pyridyl)-5-phenylisoxazole, which exhibited maximal anti-aggregatory activity among the synthesized compounds, inhibited neither cyclooxygenase nor thromboxane synthase. The compounds affected the signal transduction pathway at/or posterior to the stage of thromboxane A₂ reception.

【 授权许可】

Unknown