Department of Chemistry, Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.
Department of Chemistry, Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia; Faculty of Biology and Biotechnologies, Higher School of Economics, Myasnitskaya 13, 101000 Moscow, Russia.
Bioorg Chem. 2020 Jul;100:103900. doi: 10.1016/j.bioorg.2020.103900. Epub 2020 May 11.
Three new and complementary approaches to S-arylation of 2-thiohydantoins have been developed: copper-catalyzed cross coupling with either arylboronic acids or aryl iodides under mild conditions, or direct nucleophilic substitution in activated aryl halides. For 38 diverse compounds, reaction yields for all three methods have been determined. Selected by molecular docking, they have been tested on androgen receptor activation, and p53-Mdm2 regulation, and A549, MCF7, VA13, HEK293T, PC3, LnCAP cell lines for cytotoxicity, Two of them turned out to be promising as androgen receptor activators (likely by allosteric regulation), and another one is shown to activate the p53 cascade. It is hoped that 2-thiohydantoin S-arylidenes are worth further studies as biologically active compounds.
三种新的且互补的 2-硫代海因 S-芳基化方法得到了发展：在温和条件下，铜催化与芳基硼酸或芳基碘化物的交叉偶联，或在活化的芳基卤化物中进行直接亲核取代。对于 38 种不同的化合物，已经确定了所有三种方法的反应产率。通过分子对接进行选择，它们已经在雄激素受体激活、p53-Mdm2 调节以及 A549、MCF7、VA13、HEK293T、PC3 和 LnCAP 细胞系中的细胞毒性方面进行了测试。其中两种化合物有望作为雄激素受体激活剂（可能通过别构调节），另一种则显示出能够激活 p53 级联反应。希望 2-硫代海因 S-亚烯基物能够作为具有生物活性的化合物进一步得到研究。
