设计、合成及 4-(4-苄氧基)苯氧基哌啶类化合物作为选择性和可逆的 LSD1 抑制剂的生物活性。
Design, synthesis and biological activity of 4-(4-benzyloxy)phenoxypiperidines as selective and reversible LSD1 inhibitors.
机构信息
Department of Pharmaceutical Engineering & Department of Biochemical Engineering, 639 Longmian Avenue, Nanjing 211198, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Laboratory of Epigenetics, Institute of Biochemical Sciences, Fudan University, 131 Dong'An Road, Shanghai 200032, PR China.
出版信息
Bioorg Chem. 2018 Aug;78:7-16. doi: 10.1016/j.bioorg.2018.02.016. Epub 2018 Feb 16.
Lysine specific demethylase 1 (LSD1) plays a vital role in epigenetic regulation of gene activation and repression in several human cancers and is recognized as a promising antitumor therapeutic target. In this paper, a series of 4-(4-benzyloxy)phenoxypiperidines were synthesized and evaluated. Among the tested compounds, compound 10d exhibited the potent and reversible inhibitory activity against LSD1 in vitro (IC = 4 μM). Molecular docking was conducted to predict its binding mode. Furthermore, 10d displayed it could inhibit migration of HCT-116 colon cancer cells and A549 lung cancer cells. Taken together, 10d deserves further investigation as a hit-to-lead for the treatment of LSD1 associated tumors.
赖氨酸特异性去甲基化酶 1（LSD1）在几种人类癌症的基因激活和抑制的表观遗传调控中起着至关重要的作用，被认为是一种很有前途的抗肿瘤治疗靶点。在本文中，合成并评价了一系列 4-（4-苄氧基）苯氧基哌啶。在所测试的化合物中，化合物 10d 在体外对 LSD1 表现出强大且可逆的抑制活性（IC = 4 μM）。进行了分子对接以预测其结合模式。此外，10d 显示它可以抑制 HCT-116 结肠癌细胞和 A549 肺癌细胞的迁移。综上所述，10d 值得进一步研究，作为 LSD1 相关肿瘤治疗的先导化合物。
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