Synthesis and biological activity of 5-aryliden-2-thiohydantoin S-aryl derivatives.
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
Protein Interaction Maps
/ drug effects
Proto-Oncogene Proteins c-mdm2
/ metabolism
Receptors, Androgen
/ metabolism
Thiohydantoins
/ chemical synthesis
Tumor Suppressor Protein p53
/ metabolism
2-Thiohydantoins
Androgen receptor
Aryliodides
Boronic acids
Chan−Evans−Lam reaction
Cross coupling
Cytotoxicity
In vitro
MDM2
Molecular docking
Nucleophilic substitution
Open flask
P53
S-arylation
Ullmann-type
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
04
09
2019
revised:
24
03
2020
accepted:
28
04
2020
pubmed:
20
5
2020
medline:
4
3
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32428745
pii: S0045-2068(19)31469-5
doi: 10.1016/j.bioorg.2020.103900
pii:
doi:
Substances chimiques
Androgens
0
Antineoplastic Agents
0
Receptors, Androgen
0
Thiohydantoins
0
Tumor Suppressor Protein p53
0
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103900Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no conflict of interest.