Inhibition of mural thrombus formation by novel nipecotoylpiperazine antiplatelet agents.
The effectiveness of two closely related nipecotoylpiperazine derivatives, BPAT-143 and BPAT-117, as antiplatelet agents was measured by their ability to inhibit the accumulation of human blood platelets on collagen-coated (type 1) glass in a parallel plate flow chamber. Whole human blood, with fluorescently labeled platelets, was perfused through the flow chamber, and epi-fluorescent video microscopy was used to visualize the dynamics of individual platelet adhesion and thrombus formation on the collagen-coated surface. Digital image processing was used to analyze the dynamics of thrombus growth on the surfaces. The collagen-coated surface serves as a model for the damaged blood vessel wall, as collagen is a primary component of the matrix beneath endothelial cells. At a concentration of 50 microM, BPAT-117 (the considerably more hydrophobic molecule) inhibited platelet accumulation by striking 90 +/- 2% (+/- S.E.), while it took 2- to 4-fold higher concentrations of BPAT-143 to register meaningful to comparable effects (52 +/- 6% and 80 +/- 4%, respectively). This further corroborates the substantial impact of hydrophobic features within the matrix of appropriately structured molecules on their ability to alter platelet function.
Owens
C K
CK
Department of Chemical Engineering, Rice University, Houston, Texas 77251.
McIntire
L V
LV
Lasslo
A
A
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002452:Cell Count; D003094:Collagen; D006801:Humans; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009557:Nipecotic Acids / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014741:Video Recording
D009557:Nipecotic Acids; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; C063976:N,N'-bis(1-decylnipecotoyl)piperazine; C064604:N,N'-bis(1-hexylnipecotoyl)piperazine