Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors.
Aniline Compounds
/ chemical synthesis
Apoptosis
/ drug effects
Aurora Kinase A
/ chemistry
Binding Sites
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cyclic N-Oxides
/ chemical synthesis
G2 Phase Cell Cycle Checkpoints
/ drug effects
Humans
Molecular Docking Simulation
Piperidines
/ chemical synthesis
Protein Kinase Inhibitors
/ chemical synthesis
Pyrimidines
/ chemical synthesis
Spindle Apparatus
/ drug effects
Anticancer agents
Aurora kinases
Pyrimidine
Stable nitroxides
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
19
09
2018
revised:
16
10
2018
accepted:
05
11
2018
pubmed:
7
12
2018
medline:
18
10
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.
Identifiants
pubmed: 30502115
pii: S0968-0896(18)31634-1
doi: 10.1016/j.bmc.2018.11.006
pii:
doi:
Substances chimiques
Aniline Compounds
0
Cyclic N-Oxides
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Aurora Kinase A
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-78Informations de copyright
Copyright © 2018. Published by Elsevier Ltd.