Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Zografou, 15701 Athens, Greece.
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
Bioorg Med Chem Lett. 2019 May 1;29(9):1085-1089. doi: 10.1016/j.bmcl.2019.02.032. Epub 2019 Feb 27.
Targeted covalent inhibitors of urease were developed on the basis of the catechol structure. Forty amide and ester derivatives of 3,4-dihydroxyphenylacetic acid, caffeic acid, ferulic acid and gallic acid were obtained and screened against Sporosarcinia pasteurii urease. The most active compound, namely propargyl ester of 3,4-dihydroxyphenylacetic acid exhibited IC = 518 nM andk/K = 1379 M s. Inhibitory activity of this compound was better and toxicity lower than those obtained for the starting compound - catechol. The molecular modelling studies revealed a mode of binding consistent with structure-activity relationships.
基于儿茶酚结构，开发了靶向脲酶的共价抑制剂。得到了 3,4-二羟基苯乙酸、咖啡酸、阿魏酸和没食子酸的 40 个酰胺和酯衍生物，并对巴斯德氏固氮螺菌脲酶进行了筛选。最活跃的化合物，即 3,4-二羟基苯乙酸的炔丙酯，表现出 IC=518 nM 和 k/K=1379 M s。与起始化合物儿茶酚相比，该化合物的抑制活性更好，毒性更低。分子建模研究揭示了一种与构效关系一致的结合模式。
