Biology Project Abstract
ANTICOAGULANT, ANTIPLATELET, AND ANTIPROTEASE EFFECTS OF A NEW ANTICOAGULANT DRUG (PI-88)
Presenter:
Jessica Dy-Johnson, Illinois Mathematics and Science Academy, 1500 W. Sullivan Road, Aurora, IL 60506
Pranay Patel, Illinois Mathematics and Science Academy, 1500 W. Sullivan Road, Aurora, IL 60506
Mentors:
Jawed Fareed, Ph.D., Department of Pathology, Loyola University Medical Center, Maywood, IL 60513
Debra Hoppensteadt, Ph.D., Department of Pathology, Loyola University Medical Center, Maywood, IL 60513
Abstract:
PI-88 (Progen Industries, Ltd, Brisbane, Australia) was developed as an anticoagulant and antiproliferative agent. The purpose of this study was to determine the molecular weight profile, fractionation of parent compound and the anticoagulant potency of PI-88. The gel permeation chromatography and polyacrylamide gel electrophoresis analyses were used to determine the molecular profile and separation of components of PI-88, respectively. Potentiation of antithrombin III and HC-II activity was measured by using the chromogenic substrate assay. In order to determine anticoagulant, antiplatelet, and antiprotease effects of PI-88, various global anticoagulant tests were used. Anti-Xa and anti-IIa activities were also measured by amidolytic assays. The HPLC profiles of PI-88 showed that the average molecular weight of PI-88 is approximately 2100 Da. This agent activates HC-II for inhibiting the thrombin generation but not AT III. Although PI-88 produced a concentration dependent prolongation of all of the clotting tests, ECT gave a good correlation in the dose-response curve. PI-88 exhibited marked inhibition of FIIa but not FXa. Only in thrombin induced platelet aggregation was an effect on PI-88 observed. These results suggest that PI-88 exhibited strong antithrombotic and anticoagulant activity beside the antiproliferative properties. Because of this dual nature of the pharmacologic action of PI-88, it represents an attractive pharmacologic agent for the control of thrombotic and proliferative disorders.