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
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-...
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MDPI AG
2017-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/1/59 |
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| author | Mehlika Dilek Altıntop Halil Ibrahim Ciftci Mohamed O. Radwan Belgin Sever Zafer Asım Kaplancıklı Taha F. S. Ali Ryoko Koga Mikako Fujita Masami Otsuka Ahmet Özdemir |
| author_facet | Mehlika Dilek Altıntop Halil Ibrahim Ciftci Mohamed O. Radwan Belgin Sever Zafer Asım Kaplancıklı Taha F. S. Ali Ryoko Koga Mikako Fujita Masami Otsuka Ahmet Özdemir |
| author_sort | Mehlika Dilek Altıntop |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T11:53:38Z |
| format | Article |
| id | doaj.art-45360e46c72b47998d4dedb088801872 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T11:53:38Z |
| publishDate | 2017-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-45360e46c72b47998d4dedb0888018722022-12-21T17:48:08ZengMDPI AGMolecules1420-30492017-12-012315910.3390/molecules23010059molecules23010059Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole MoietyMehlika Dilek Altıntop0Halil Ibrahim Ciftci1Mohamed O. Radwan2Belgin Sever3Zafer Asım Kaplancıklı4Taha F. S. Ali5Ryoko Koga6Mikako Fujita7Masami Otsuka8Ahmet Özdemir9Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyDepartment of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanResearch Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Bioorganic Medicinal Chemistry, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, TurkeyIn 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.https://www.mdpi.com/1420-3049/23/1/59thiadiazolethiazolebenzothiazoleBcr-Ablkinase inhibitorleukemia |
| spellingShingle | Mehlika Dilek Altıntop Halil Ibrahim Ciftci Mohamed O. Radwan Belgin Sever Zafer Asım Kaplancıklı Taha F. S. Ali Ryoko Koga Mikako Fujita Masami Otsuka Ahmet Özdemir 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 Molecules thiadiazole thiazole benzothiazole Bcr-Abl kinase inhibitor leukemia |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | thiadiazole thiazole benzothiazole Bcr-Abl kinase inhibitor leukemia |
| url | https://www.mdpi.com/1420-3049/23/1/59 |
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