1. Synthesis and biological activity of 5-aryliden-2-thiohydantoin S-aryl derivatives.
- Author
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Finko AV, Skvortsov DA, Laikov DN, Averochkin GM, Dlin EA, Kalinina MA, Aladinskiy VA, Vorobyeva NS, Mironov AV, Beloglazkina EK, Zyk NV, Ivanenkov YA, and Majouga AG
- Subjects
- Allosteric Regulation drug effects, Androgens chemical synthesis, Antineoplastic Agents chemical synthesis, Cell Line, Tumor, Cell Survival drug effects, Chemistry Techniques, Synthetic, HEK293 Cells, Humans, Molecular Docking Simulation, Neoplasms drug therapy, Neoplasms metabolism, Protein Interaction Maps drug effects, Proto-Oncogene Proteins c-mdm2 metabolism, Receptors, Androgen metabolism, Thiohydantoins chemical synthesis, Tumor Suppressor Protein p53 metabolism, Androgens chemistry, Androgens pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Thiohydantoins chemistry, Thiohydantoins pharmacology
- Abstract
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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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