Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety

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Altıntop M. D., Ciftci H. I., Radwan M. O., Sever B., Kaplancıklı Z. A., Ali T. F. S., ...More

MOLECULES, vol.23, no.1, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 1
  • Publication Date: 2018
  • Doi Number: 10.3390/molecules23010059
  • Journal Name: MOLECULES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: thiadiazole, thiazole, benzothiazole, Bcr-Abl, kinase inhibitor, leukemia, INHIBITORS, CANCER, RESISTANCE, MOLECULES, 1,3,4-OXADIAZOLE, BENZOTHIAZOLES, DISCOVERY, THIAZOLE, ABL
  • Anadolu University Affiliated: Yes


In an attempt to develop potent antitumor agents, new 1,3,4-thiadiazole derivatives were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the K562 chronic myelogenous leukemia cell line that expresses the Bcr-Abl tyrosine kinase. N-(5-Nitrothiazol-2-yl)-2-((5-((4-(trifluoromethyl)phenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide (2) inhibited the Abl protein kinase with an IC50 value of 7.4 mu M and showed selective activity against the Bcr-Abl positive K562 cell line. Furthermore, a Bcr-Abl-compound 2 molecular modelling simulation highlighted the anchoring role of the nitrothiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. These results provide promising starting points for further development of novel kinase inhibitors.