TY  - JOUR
TI  - 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
AB  - 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.
AU  - Akalin Ciftci, Gulsen
AU  - SEVER, Belgin
AU  - Altıntop, Mehlika Dilek
DO  - 10.4274/tjps.galenos.2019.2018.96658
PY  - 2019
JO  - Turkish Journal of Pharmaceutical Sciences
VL  - 16
IS  - 2
SN  - 1304-530X
SP  - 119
EP  - 131
DB  - TRDizin
UR  - http://search/yayin/detay/354182
ER  -