MOLECULES, vol.23, no.1, 2018 (SCI-Expanded)
Article / Article
Science Citation Index Expanded (SCI-EXPANDED), Scopus
thiadiazole, thiazole, benzothiazole, Bcr-Abl, kinase inhibitor, leukemia, INHIBITORS, CANCER, RESISTANCE, MOLECULES, 1,3,4-OXADIAZOLE, BENZOTHIAZOLES, DISCOVERY, THIAZOLE, ABL
Anadolu University Affiliated:
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.