Yeni platelet inhibitörü tuzların ilaç etkin maddesi olarak geliştirilmesi ve aktivitelerinin araştırılması
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Bu çalışmada ülkemizde üretimi olmayan aktif farmasötik bileşen geliştirilmesi, Üniversite-Sanayi işbirliğinde ilaç adayı olabilecek yeni bir molekülün ortak araştırmalar sonucu ortaya konulması istenmiştir. Bu tez kapsamında Prasugrel'in, çeşitli karşıt iyonlarla reaksiyonu sonucunda 2'si yeni 5 farklı Prasugrel tuzu elde edilmiş, yapıları ve saflıkları spektroskopik yöntemler ve eleman analizi verileriyle kanıtlanmıştır. Materyal ve Metot: Prasugrel tuzlarının in vitro antiplatelet ve antikanser aktiviteleri araştırılmış ve diyabette artan aterotromboz etkisini anlayabilmek için diyabetik ve nondiyabetik hayvanlarda in vivo-ex vivo antiplatelet aktiviteleri karşılaştırılmıştır. Ex vivo ölçümlerde Chrono-Log agregometre cihazı ile sitratlı tam kanda antiagregan aktivite belirlenmiştir. Trombosit aktivasyon yolağında yer alan bileşenlerin, serumdan ve tam kandan izole edilen trombositlerde ELISA tekniği ile ölçümü yapılmıştır. In vitro antiplatelet ve antikanser çalışmalarında ELISA kitleri kullanılmıştır. Bulgular: In vivo-ex vivo çalışmalarda ADP için 4a Prasugrel'e göre daha zayıf etkili 2a ve 3a daha yüksek etkili, epinefrin için 2a yüksek etkili bulunmuştur. 1a, 2a, 3a ve 4a tarafından TxB2 ve GpIIb/IIIa düzeyleri diyabetik gruplarda anlamlı biçimde inhibe edilmiştir. pAKT ve pERK2 ölçümlerinde, nondiyabetik gruplarda 1a, 2a, 3a ve 4a tarafından yüksek inhibisyon gerçekleşmiştir. VASP düzeyi için nondiyabetiklerde 2a anlamlı bir azalmaya neden olmuştur. In vitro antiplatelet ve antikanser çalışmalarında aktivite gözlenememiştir. Sonuçlar: In vivo-ex vivo çalışmalarda 2a ve 3a için baz Prasugrel'e yakın veya daha güçlü antiplatelet aktivite gözlenmiştir. In vitro antiplatelet ve antikanser çalışmalarında aktivite gözlenememiştir. Anahtar Sözcükler: Prasugrel, Tuz, Antiplatelet, Diyabet, Antikanser
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
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
Açıklama
Anahtar Kelimeler
Eczacılık ve Farmakoloji, Pharmacy and Pharmacology
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Scopus Q Değeri
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Künye
Uslu, H. (2018). Yeni platelet inhibitörü tuzların ilaç etkin maddesi olarak geliştirilmesi ve aktivitelerinin araştırılması. Yayımlanmış Doktora lisans tezi, İnönü Üniversitesi, Malatya.
