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.