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STUDIES TOWARDS HEMOCOMPATIBILITY OF POLYAMINE CONJUGATES WITH BICYCLIC SYSTEMS

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Szumilak M., Markowicz-Piasecka M., Mikiciuk-Olasik E., Stanczak A., Sikora J.
Acta Poloniae Pharmaceutica - Drug Research
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2018
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vol. 75
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issue 4
861-874
EN
Assessing hemocompatibility of anticancer drug candidate is very important task due to the fact that coagulation disorders are often correlated with malignancy or induced by chemotherapy. The aim of this study was to examine the influence of some polyamine conjugates with bicyclic systems on the process of coagulation and fibrinolysis. In addition their effect on the healthy human erythrocytes (RBCs) was assessed. Prothrombin Time (PT), Activated Partial Tromboplastin Time (APTT), clot formation and lysis test (CL-test) were performed to evaluate the influence of some polyamine conjugates on plasma hemostasis. The effects of tested compounds on RBCs were assessed using hemolysis assays and microscopy studies. APTT and PT examination revealed that all tested compounds apart from the highest concentrations of compounds 3 and 5 did not exert significant effects on intrinsic and extrinsic coagulation pathways. Despite their substantial influence on the kinetic parameters of the process of clot formation and fibrinolysis, the examined compounds, over the entire concentration range, did not alter the overall potential of clot formation and lysis (CLAUC) suggesting that they might be regarded as biocompatible concerning plasma hemostasis. At potential therapeutic concentrations (constituting IC50 value for MCF-7 cells) tested polyamine conjugates showed no adverse effects on the membranes of RBCs. Promising antiproliferative activity of representative polyamine conjugates together with their hemocompatibility make them good anticancer drug candidates for further preclinical evaluation.
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