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
-
- Mehlika Altıntop
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
-
- Halil Ciftci
- Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Mohamed Radwan
- Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Belgin Sever
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
-
- Zafer Kaplancıklı
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
-
- Taha Ali
- Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Ryoko Koga
- Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Mikako Fujita
- Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Masami Otsuka
- Department of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan
-
- Ahmet Özdemir
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
説明
<jats:p>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.</jats:p>
収録刊行物
-
- Molecules
-
Molecules 23 (1), 59-, 2017-12-27
MDPI AG
