2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile as novel inhibitor of receptor tyrosine kinase and PI3K/AKT/mTOR signaling pathway in glioblastoma.
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
G1 Phase Cell Cycle Checkpoints
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Glioblastoma
/ pathology
Humans
Nitriles
/ chemistry
Phosphatidylinositol 3-Kinases
/ metabolism
Protein Kinase Inhibitors
/ chemistry
Proto-Oncogene Proteins c-akt
/ metabolism
Receptor Protein-Tyrosine Kinases
/ antagonists & inhibitors
S Phase Cell Cycle Checkpoints
/ drug effects
Signal Transduction
/ drug effects
TOR Serine-Threonine Kinases
/ metabolism
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Mar 2019
15 Mar 2019
Historique:
received:
16
11
2018
revised:
09
01
2019
accepted:
09
01
2019
pubmed:
8
2
2019
medline:
27
3
2019
entrez:
8
2
2019
Statut:
ppublish
Résumé
Nerve growth factor receptor (NGFR), a member of kinase protein, is emerging as an important target for Glioblastoma (GBM) treatment. Overexpression of NGFR is observed in many metastatic cancers including GBM, promoting tumor migration and invasion. Hydrazones have been reported to effectively interact with receptor tyrosine kinases (RTKs). We report herein the synthesis of 23 arylhydrazones of active methylene compounds (AHAMCs) compounds and their anti-proliferative activity against GBM cell lines, LN229 and U87. Compound R234, 2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile, was identified as the most active anti-neoplastic compound, with the IC
Identifiants
pubmed: 30731398
pii: S0223-5234(19)30031-5
doi: 10.1016/j.ejmech.2019.01.021
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Nitriles
0
Protein Kinase Inhibitors
0
benzonitrile
9V9APP5H5S
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
291-303Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.