• About
  • Policies
  • What is open access
  • Library
  • Contact
Advanced search
      View Item 
      •   BUIR Home
      • Scholarly Publications
      • Faculty of Science
      • Department of Molecular Biology and Genetics
      • View Item
      •   BUIR Home
      • Scholarly Publications
      • Faculty of Science
      • Department of Molecular Biology and Genetics
      • View Item
      JavaScript is disabled for your browser. Some features of this site may not work without it.

      Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins

      Thumbnail
      View / Download
      2.6 Mb
      Author(s)
      Aytaç, P. S.
      Durmaz, I.
      Houston, D. R.
      Çetin-Atalay R.
      Tozkoparan, B.
      Date
      2016
      Source Title
      Bioorganic and Medicinal Chemistry
      Print ISSN
      0968-0896
      Publisher
      Elsevier
      Volume
      24
      Issue
      4
      Pages
      858 - 872
      Language
      English
      Type
      Article
      Item Usage Stats
      143
      views
      186
      downloads
      Abstract
      Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then ∼5 μM (IC50) were further analyzed and showed to induce apoptotic cell death and SubG1cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3β, β-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. © 2016 Published by Elsevier Ltd.
      Keywords
      Aminomercaptotriazole
      Apoptosis
      Cytotoxic activity
      Oxidative stress
      Triazolothiadiazine
      Permalink
      http://hdl.handle.net/11693/36870
      Published Version (Please cite this version)
      http://dx.doi.org/10.1016/j.bmc.2016.01.013
      Collections
      • Department of Molecular Biology and Genetics 468
      Show full item record

      Browse

      All of BUIRCommunities & CollectionsTitlesAuthorsAdvisorsBy Issue DateKeywordsTypeDepartmentsThis CollectionTitlesAuthorsAdvisorsBy Issue DateKeywordsTypeDepartments

      My Account

      LoginRegister

      Statistics

      View Usage StatisticsView Google Analytics Statistics

      Bilkent University

      If you have trouble accessing this page and need to request an alternate format, contact the site administrator. Phone: (312) 290 1771
      © Bilkent University - Library IT

      Contact Us | Send Feedback | Off-Campus Access | Admin | Privacy