İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi

Güneş, Yakup; Ciftci, Mehmet; Akkemik, Ebru

İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi

Yürütücü

Ebru AKKEMİK (Siirt Üniversitesi, Mühendislik Mimarlık Fakültesi, Gıda Mühendisliği Bölümü, Siirt, Türkiye)

Danışman(lar)

Mehmet ÇİFTÇİ (Girilmedi)

Araştırmacı(lar)

Yakup GÜNEŞ (Adres Yazılmamış)

15 1

Proje Grubu: KBAG Sayfa Sayısı: 129 Proje No: 115Z773 Proje Bitiş Tarihi: 15.06.2017 Metin Dili: Türkçe İndeks Tarihi: 24-01-2020

İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi

Öz:

Bu çalışmada temel amaç kanserle doğrudan ilişkili olduğu düşünülen Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) enzimlerinin potansiyel inhibitör/aktivatörlerini sentezlemektir. Günümüzün vebası haline gelen kanser, gün geçtikçe daha çok insanı etkisi altına almaktadır. Bu nedenle birçok araştırmacı çalışmalarını antikanser ajanlar ve kanser tedavisiyle ilgili alanlara yönlendirmektedir. Yapılan her çalışma, kanser oluşumu ve sürecinin ne kadar karmaşık olduğunu göstermektedir. Kanser etmenlerinden biri olarak kabul edilen TrxR?nin ise tümörlü hücrelerde aşırı bir şekilde eksprese olarak, tümör hücrelerinin gelişimine yol açtığı ayrıca söz konusu enzimin apoptosisle de bağlantılı olduğu tespit edilmiştir. PKM2 enziminin de kanserli hücrelerde aşırı derecede eksprese olduğu ve bu şekilde kanserli hücrelerin enerji ihtiyacını karşıladığı bilinmektedir. Son yapılan çalışmalarda PKM2 enziminin aktivatörlerinin de antiproliferatif ajan olarak kullanılabileceği belirtilmiştir. Metabolizma üzerinde belirtilen fizyolojik önemleri sebebiyle TrxR ve PKM2 enzimleri, bu araştırmanın odak noktasını oluşturmaktadır. Kiral imin bileşikleri, dialdehitler ile kiral aminler arasındaki reaksiyondan sentezlendi. Elde edilen 10 farklı imin bileşiği 1H-,13C-NMR, FTIR, Q-TOF LC/MS ve termal analiz metotları ile karakterize edildi. Sentezlenen bileşiklerin sekiz farklı yöntemle antioksidan özellikleri spektrofotometrik olarak belirlendi. Bunun sonucunda 10 bileşiğinde en az bir yöntemde antioksidan özellik gösterdiği tespit edildi. Ayrıca bu bileşiklerin in vitro şartlarda PKM-2 ve TrxR için inhibisyon etkisi araştırıldı. İn vitro şartlarda TrxR enzim aktivitesi üzerinde en yüksek inhibisyonu AS6 (IC50 15,85 μM) bileşiğinin sağladığı, PKM-2 enzim aktivitesi üzerinde en yüksek inhibisyonu ise CS8 (IC50 4,34 μM) bileşiğinin sağladığı tespit edildi. Son olarak CS3 (AC50 26,18 μM) bileşiğinin PKM-2 enzim aktivitesi üzerinde aktivasyon etkisi gösterdiği belirlendi. CS3, AS6 ve CS8 için MCF7, ATCC HTB-22 hücrelerinde MTT Yöntemi ile antikanser çalışması yapıldı. İn vitro çalışmalar sonucu elde edilen veriler ışığında CS3, AS6 ve CS8?in Wistar Albino Rat?lar üzerinde in vivo çalışmaları gerçekleştirildi. Sıçanların karaciğer, böbrek, beyin, kas ve akciğerlerinde piruvat kinaz ve tiyoredoksin redüktaz enzim aktiviteleri incelendi. Her bir dokuda kontrol aktivitesi 100 kabul edilerek, AS6 uygulanmış sıçanların beyin, kas, böbrek, karaciğer ve akciğer dokularında TrxR aktiviteleri kıyasladığında sırasıyla aktvitenin %86.56, %108.83, %84.41, %80.78 ve %41.38 olarak değiştiği tespit edildi. CS3 uygulanmış sıçanlarn beyin, kas, böbrek, karaciğer ve akciğer dokularında Piruvat Kinaz enzim aktiviteleri kıyaslandığında enzim aktivitesinin sırasıyla %37.84, %6.19, %62.46, %304, %160 olarak değiştiği tespit edildi. CS8 uygulanmış sıçanların beyin, kas, böbrek, karaciğer ve akciğer dokularında Piruvat Kinaz enzim aktiviteleri kıyasladığında enzim aktivitesinin sırasıyla %25.23, %12.46, %19.37, %87.38, %62.86 şeklinde değiştiği tespit edildi.

Anahtar Kelime: Piruvat Kinaz M2 ve kanser Tiyoredoksin Redüktaz antioksidan İmin bileşikleri

Konular: Biyoloji Kimya, Uygulamalı Kimya, Organik Kimya, Tıbbi

Erişim Türü: Erişime Açık

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APA	Akkemik E, Ciftci M, Güneş Y (2017). İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. , 1 - 129.
Chicago	Akkemik Ebru,Ciftci Mehmet,Güneş Yakup İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. (2017): 1 - 129.
MLA	Akkemik Ebru,Ciftci Mehmet,Güneş Yakup İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. , 2017, ss.1 - 129.
AMA	Akkemik E,Ciftci M,Güneş Y İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. . 2017; 1 - 129.
Vancouver	Akkemik E,Ciftci M,Güneş Y İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. . 2017; 1 - 129.
IEEE	Akkemik E,Ciftci M,Güneş Y "İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi." , ss.1 - 129, 2017.
ISNAD	Akkemik, Ebru vd. "İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi". (2017), 1-129.

APA	Akkemik E, Ciftci M, Güneş Y (2017). İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. , 1 - 129.
Chicago	Akkemik Ebru,Ciftci Mehmet,Güneş Yakup İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. (2017): 1 - 129.
MLA	Akkemik Ebru,Ciftci Mehmet,Güneş Yakup İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. , 2017, ss.1 - 129.
AMA	Akkemik E,Ciftci M,Güneş Y İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. . 2017; 1 - 129.
Vancouver	Akkemik E,Ciftci M,Güneş Y İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi. . 2017; 1 - 129.
IEEE	Akkemik E,Ciftci M,Güneş Y "İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi." , ss.1 - 129, 2017.
ISNAD	Akkemik, Ebru vd. "İn vitro ve İn vivo Şartlarda Tiyoredoksin Redüktaz (TrxR) ve Piruvat Kinaz M2 (PKM2) Enzim Aktiviteleri Üzerine Bazı Yeni İmin Bileşiklerinin Etkisinin İncelenmesi". (2017), 1-129.