Daśko Mateusz, Rachon Janusz, Masłyk Maciej, Kubiński Konrad, Demkowicz Sebastian
Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland.
Department of Molecular Biology, Faculty of Biotechnology and Environmental Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland.
Chem Biol Drug Des. 2017 Jul;90(1):156-161. doi: 10.1111/cbdd.12931. Epub 2017 Feb 7.
Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C-F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC value of 2.18 μm (IC value of 2.13 μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.
类固醇硫酸酯酶（STS）负责将生物活性硫酸化类固醇水解为其活性非硫酸化形式，并促进各种激素依赖性癌症（如乳腺癌）的生长。因此，STS酶是治疗类固醇敏感癌症的一个有前景的治疗靶点。在此，我们报告了基于含C-F键的N-酰化酪胺的氨基磺酸酯类似物作为潜在STS抑制剂的合成及生物学评价。使用从人胎盘中分离的STS测试了这些类似物的抑制作用。在所测试的类似物中，4-(2-全氟十一烷酰氨基乙基)-苯氨基磺酸酯（5r）表现出最大的抑制作用，IC值为2.18μm（以香豆素-7-O-氨基磺酸酯的IC值2.13μm作为参考）。我们使用分子对接技术进行的计算分析结果支持了这些发现。
