利用斑马鱼模型鉴定新型芳香烃受体 (AhR) 拮抗剂。
Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model.
机构信息
Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
出版信息
Bioorg Med Chem. 2019 Oct 1;27(19):115014. doi: 10.1016/j.bmc.2019.07.030. Epub 2019 Jul 18.
A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.
合成了一系列新的 1,3-二酮、杂环和α,β-不饱和衍生物，并利用斑马鱼和哺乳动物细胞评估了它们对 AhR 拮抗剂的活性。化合物 1b、2c、3b 和 5b 在转基因斑马鱼模型中表现出显著的 AhR 拮抗剂活性。其中，化合物 3b 和 5b 在荧光素酶报告基因检测中表现出优异的 AhR 拮抗剂活性，IC 分别为 3.36nM 和 8.3nM。在干细胞增殖试验中，化合物 5b 引起明显的 HSC 扩增。
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