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

• Ngôn ngữ: eng
• Ký hiệu phân loại: 547.3 Analytical organic chemistry
• Thông tin xuất bản: Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2017
• Mô tả vật lý: Size: Article No. 59 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260304
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 59 basic biological sciences; 3. 60 applied life sciences; 4. Bcr-abl; 5. Benzothiazole; 6. Kinase inhibitor; 7. Leukemia; 8. Thiadiazole; 9. Thiazole

Tóm tắt

 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 IC<
 sub>
 50<
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  value of 7.4 �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.