A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells
Yıl: 2019 Cilt: 16 Sayı: 2 Sayfa Aralığı: 119 - 131 Metin Dili: İngilizce DOI: 10.4274/tjps.galenos.2019.2018.96658 İndeks Tarihi: 25-08-2020
A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells
Öz: Objectives: Akt is considered as an attractive target for anticancer drug discovery and development and therefore extensive efforts have beendevoted to the discovery of new potent anticancer agents targeting Akt.Materials and Methods: Due to the importance of thiadiazoles for anticancer drug discovery, herein eight 1,3,4-thiadiazole derivatives wereinvestigated for their cytotoxic effects on C6 rat glioma and A549 human lung adenocarcinoma cell lines using the MTT assay. The effects of themost promising anticancer agents on apoptosis, caspase-3 activation, mitochondrial membrane potential, and cell cycle arrest were determinedon a BD FACSAria (I) flow cytometer. Akt activity was measured in the C6 and A549 cell lines using an ELISA colorimetric method. Schrödinger’sMaestro molecular modeling package was used to explore the possible binding modes of compounds 3 and 8 in the active site of Akt enzyme (PDBcode: 3OW4).Results: N-(4-Chlorophenyl)-2-[(5-((4-nitrophenyl)amino)-1,3,4-thiadiazol-2-yl)thio]acetamide (3) and N-(6-nitrobenzothiazol-2-yl)-2-[(5-((4-nitrophenyl)amino)-1,3,4-thiadiazol-2-yl)thio]acetamide (8) induced apoptosis and cell cycle arrest in the C6 cell line through inhibition of Aktactivity (92.36% and 86.52%, respectively). The docking results of compounds 3 and 8 indicated that π-π interactions, H bonds, and salt-bridgeformation were responsible for the observed Akt inhibitory activity.Conclusion: According to in vitro and docking studies, compounds 3 and 8 stand out as promising antiglioma agents.
Anahtar Kelime: Akciğer Adenokarsinom ve Glioma Hücrelerinde Akt Aktivitesinin Bastırılması Yoluyla Hücre Döngüsü Arrestini ve Apoptozu İndükleyen Tiyadiazol Türevi Antikanser Ajanlar Üzerine Kapsamlı Bir Çalışma
Öz: Amaç: Akt, antikanser ilaç keşfinde ve gelişiminde önemli bir hedef olarak düşünülmektedir ve bu nedenle Akt enzimini hedefleyen yeni potent antikanser ajanların keşfi için yoğun çaba harcanmıştır. Gereç ve Yöntemler: Tiyadiazollerin antikanser ilaç keşfindeki önemine bağlı olarak, bu çalışmada sekiz adet 1,3,4-tiyadiazol türevinin C6 sıçan glioma ve A549 insan akciğer adenokarsinoma hücre dizileri üzerindeki sitotoksik etkileri MTT deneyi kullanılarak araştırılmıştır. En etkili antikanser ajanların apoptoz, kaspaz-3 aktivasyonu, mitokondriyal membran potansiyeli, hücre döngüsü arresti üzerindeki etkileri BD FACSAria (I) akış sitometrisi ile belirlenmiştir. Akt aktivite, C6 ve A549 hücre dizilerinde ELISA kolorimetrik yöntem kullanılarak ölçülmüştür. 3 ve 8 no’lu bileşiklerin Akt enziminin (PDB kod: 3OW4) aktif bölgesindeki olası bağlanma biçimlerini araştırmak için Schrödinger’s Maestro moleküler modelleme programı kullanılmıştır. Bulgular: N-(4-Klorofenil)-2-[(5-((4-nitrofenil)amino)-1,3,4-tiyadiazol-2-il)tiyo]asetamit (3) ve N-(6-nitrobenzotiyazol-2-il)-2-[(5-((4-nitrofenil) amino)-1,3,4-tiyadiazol-2-il)tiyo]asetamit (8), C6 hücre dizisinde apoptozu ve hücre döngüsü tutuklanmasını Akt aktivitesi inhibisyonu aracılığıyla(sırasıyla %92.36 ve %86.52) indüklemişlerdir. Bu bileşiklerin docking sonuçları, gözlemlenen Akt inhibitör aktiviteden π-π etkileşimleri, hidrojen bağları ve tuz köprüsü oluşumunun sorumlu olduğunu belirtmektedir. Sonuç: In vitro ve docking çalışmalarına göre, 3 ve 8 no’lu bileşikler umut vadeden antiglioma ajanlar olarak dikkat çekmektedirler.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | Akalin Ciftci G, SEVER B, Altıntop M (2019). A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. , 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| Chicago | Akalin Ciftci Gulsen,SEVER Belgin,Altıntop Mehlika Dilek A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. (2019): 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| MLA | Akalin Ciftci Gulsen,SEVER Belgin,Altıntop Mehlika Dilek A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. , 2019, ss.119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| AMA | Akalin Ciftci G,SEVER B,Altıntop M A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. . 2019; 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| Vancouver | Akalin Ciftci G,SEVER B,Altıntop M A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. . 2019; 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| IEEE | Akalin Ciftci G,SEVER B,Altıntop M "A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells." , ss.119 - 131, 2019. 10.4274/tjps.galenos.2019.2018.96658 |
| ISNAD | Akalin Ciftci, Gulsen vd. "A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells". (2019), 119-131. https://doi.org/10.4274/tjps.galenos.2019.2018.96658 |
| APA | Akalin Ciftci G, SEVER B, Altıntop M (2019). A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. Turkish Journal of Pharmaceutical Sciences, 16(2), 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| Chicago | Akalin Ciftci Gulsen,SEVER Belgin,Altıntop Mehlika Dilek A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. Turkish Journal of Pharmaceutical Sciences 16, no.2 (2019): 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| MLA | Akalin Ciftci Gulsen,SEVER Belgin,Altıntop Mehlika Dilek A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. Turkish Journal of Pharmaceutical Sciences, vol.16, no.2, 2019, ss.119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| AMA | Akalin Ciftci G,SEVER B,Altıntop M A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. Turkish Journal of Pharmaceutical Sciences. 2019; 16(2): 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| Vancouver | Akalin Ciftci G,SEVER B,Altıntop M A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells. Turkish Journal of Pharmaceutical Sciences. 2019; 16(2): 119 - 131. 10.4274/tjps.galenos.2019.2018.96658 |
| IEEE | Akalin Ciftci G,SEVER B,Altıntop M "A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells." Turkish Journal of Pharmaceutical Sciences, 16, ss.119 - 131, 2019. 10.4274/tjps.galenos.2019.2018.96658 |
| ISNAD | Akalin Ciftci, Gulsen vd. "A Comprehensive Study on Thiadiazole-Based Anticancer Agents Inducing Cell Cycle Arrest and Apoptosis/Necrosis Through Suppression of Akt Activity in Lung Adenocarcinoma and Glioma Cells". Turkish Journal of Pharmaceutical Sciences 16/2 (2019), 119-131. https://doi.org/10.4274/tjps.galenos.2019.2018.96658 |
