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Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA(1) and hA(3) Adenosine Receptor
- Title
- Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA(1) and hA(3) Adenosine Receptor
- Authors
- Park, Sujin; Ahn, Yujin; Kim, Yongchan; Roh, Eun Joo; Lee, Yoonji; Han, Chaebin; Yoo, Hee Min; Yu, Jinha
- Ewha Authors
- 유진하
- SCOPUS Author ID
- 유진하
- Issue Date
- 2022
- Journal Title
- MOLECULES
- ISSN
- 1420-3049
- Citation
- MOLECULES vol. 27, no. 13
- Keywords
- adenosine receptor; dual ligand; 1; 3; 5-triazine; molecular docking; antitumor agents
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA(1), hA(2A), hA(2B), and hA(3). Both hA(1) and hA(3) AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds 9a and 11b showed good binding affinity to both hA(1) and hA(3) AR, while 9c showed the highest binding affinity to hA(1) AR. In this study, we discovered that 9c inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 9c caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA(1) and hA(3) AR were predicted by a molecular docking study.
- DOI
- 10.3390/molecules27134016
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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molecules-27-04016-v3.pdf(4.35 MB)
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