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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

2017; Multidisciplinary Digital Publishing Institute; Volume: 23; Issue: 1 Linguagem: Inglês

10.3390/molecules23010059

1433-1373

Mehlika Dilek Altıntop, Halil I. Ciftci, Mohamed O. Radwan, Belgin Sever, Zafer Asım Kaplancıklı, Taha F. S. Ali, Ryoko Koga, Mikako Fujita, Masami Otsuka, Ahmet Özdemır,

Synthesis and Characterization of Heterocyclic Compounds

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 µM 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.