Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hA and hA Adenosine Receptor.

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, hA, hA, and hA. Both hA and hA 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 and showed good binding affinity to both hA and hA AR, while showed the highest binding affinity to hA AR. In this study, we discovered that inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that 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 and hA AR were predicted by a molecular docking study.