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设计、合成及 1,3,5-三嗪衍生物针对 hA 和 hA 腺苷受体的生物评价。

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

机构信息

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.

Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

出版信息

Molecules. 2022 Jun 22;27(13):4016. doi: 10.3390/molecules27134016.

DOI:10.3390/molecules27134016
PMID:35807265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9268102/
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, 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.

摘要

腺嘌呤核苷在体内介导各种生理活动。腺嘌呤核苷受体 (AR) 在肿瘤和肿瘤微环境 (TME) 中广泛表达，它们诱导肿瘤增殖并抑制免疫细胞功能。人类有四种腺嘌呤核苷受体 (hAR)：hA、hA、hA 和 hA。hA 和 hA AR 都在肿瘤增殖中发挥重要作用。我们通过胺化和 Suzuki 偶联设计并合成了新型 1,3,5-三嗪衍生物，并评估了它们与每种 hAR 亚型的结合亲和力。化合物 和 对 hA 和 hA AR 均表现出良好的结合亲和力，而 对 hA AR 的结合亲和力最高。在这项研究中，我们发现 抑制肺癌细胞系的细胞活力，导致细胞死亡。流式细胞术分析显示 导致细胞内活性氧 (ROS) 增加和线粒体膜电位去极化。通过分子对接研究预测了 1,3,5-三嗪衍生物与 hA 和 hA AR 的结合模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/9e313c2808a5/molecules-27-04016-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/99671638fb29/molecules-27-04016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/1c1e66482b84/molecules-27-04016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/70821eb532ff/molecules-27-04016-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/88498b39d31a/molecules-27-04016-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/cbffa3d9da95/molecules-27-04016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/19c695200253/molecules-27-04016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/dd771419b809/molecules-27-04016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/b1f56b261cba/molecules-27-04016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/9e313c2808a5/molecules-27-04016-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/99671638fb29/molecules-27-04016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/1c1e66482b84/molecules-27-04016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/70821eb532ff/molecules-27-04016-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/88498b39d31a/molecules-27-04016-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/cbffa3d9da95/molecules-27-04016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/19c695200253/molecules-27-04016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/dd771419b809/molecules-27-04016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/b1f56b261cba/molecules-27-04016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/224b/9268102/9e313c2808a5/molecules-27-04016-g007.jpg

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