Development of novel antiplatelet salts as drug active ingredients and investigation of activities

Aim: The aims of this study were to develop an API substance which is not produced in our country and to put forward the result of joint researches with a new molecule which may be a drug candidate with the cooperation of University-Industry. In this thesis, with various counter ions, 2 new of 5 different Prasugrel salts have been obtained. Prasugrel salts structure and purity have been proved by spectroscopic methods and elementel analysis. Material and Method: The in vitro antiplatelet and anticancer activities of these Prasugrel salts were investigated, and in vivo-ex vivo antiplatelet activities were compared in diabetic and nondiabetic animals in order to understand the increased atherothrombotic effect. Antiplatelet activity was determined by ex vivo measurements with total blood in citrate by using Chronolog aggregometer. The components of the platelet activation pathway were evaluated by ELISA technique in platelets isolated from serum and whole blood. In vitro antiplatelet and anticancer studies were performed using ELISA kits. Results: According to in vivo-ex vivo studies, 4a was weakly effective for ADP whereas 2a and 3a were found to be highly effective. For epinephrine, 2a was found to be highly effective. TxB2 and GpIIb/IIIa levels were significantly inhibited in diabetic groups by 1a, 2a, 3a and 4a. High inhibition by pAKT and pERK2 was observed in nondiabetic groups by 1a, 2a, 3a and 4a. In nondiabetics, 2a resulted in a significant decrease in VASP levels. Prasugrel salts, according to in vitro studies for antiplatelet and anticancer activities found to be ineffective. Conclusion: According to in vivo-ex vivo studies, antiplatelet activity closer to or greater than base Prasugrel was observed for 2a and 3a. Prasugrel salts, according to in vitro studies for antiplatelet and anticancer activities found to be ineffective. Key Words: Prasugrel, Salt, Antiplatelet, Diabetes, Anticancer