Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis.
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Hep G2 Cells
Humans
Hydrazones
/ chemistry
Isatin
/ chemistry
MCF-7 Cells
Neoplasm Metastasis
/ drug therapy
Oxidative Stress
/ drug effects
Protein Binding
Protein Kinase Inhibitors
/ pharmacology
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Triazoles
/ chemistry
Apoptosis
Cell proliferation
Isatin-triazole hydrazones
Metastasis
Microtubule affinity-regulating kinase 4
Oxidative stress
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:
01 Feb 2019
01 Feb 2019
Historique:
received:
08
11
2018
revised:
04
12
2018
accepted:
12
12
2018
pubmed:
24
12
2018
medline:
12
2
2019
entrez:
23
12
2018
Statut:
ppublish
Résumé
Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces apoptosis in these cancerous cells, with IC
Identifiants
pubmed: 30579124
pii: S0223-5234(18)31063-8
doi: 10.1016/j.ejmech.2018.12.026
pii:
doi:
Substances chimiques
Hydrazones
0
Protein Kinase Inhibitors
0
Triazoles
0
Isatin
82X95S7M06
MARK4 protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
840-852Informations de copyright
Copyright © 2018 Elsevier Masson SAS. All rights reserved.