In Silico and In Vitro Studies of Natural Compounds as Human CK2 Inhibitors.
CK2
In silico screening
cancer.
in vitro
inhibitors
natural compounds
Journal
Current computer-aided drug design
ISSN: 1875-6697
Titre abrégé: Curr Comput Aided Drug Des
Pays: United Arab Emirates
ID NLM: 101265750
Informations de publication
Date de publication:
2021
2021
Historique:
received:
07
10
2019
revised:
26
01
2020
accepted:
19
02
2020
pubmed:
13
3
2020
medline:
15
12
2021
entrez:
13
3
2020
Statut:
ppublish
Résumé
Casein Kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase with broad spectrum of substrates. This enzyme is widely expressed in eukaryotic cells and is overexpressed in different human cancers. Thus, the inhibition of CK2 can induce the physiological process of apoptosis leading to tumor cell death. Selecting natural inhibitors toward the target enzyme using database mining. With our continuous effort to discover new compounds with CK2 inhibitory effect, several commercial natural databases were searched using molecular modeling approach and the selected compounds were evaluated in vitro. Three compounds were selected as candidates and evaluated in vitro using CK2 holoenzyme, their effect on three cancer cell lines was determined. The selected candidates were weak inhibitors toward the target enzyme, only one compound showed moderate effect on cell viability. Several natural databases were screened, compounds were selected and tested in vitro. Despite the unexpected low inhibitory activity of the tested compounds, this study can help in directing the search of potent CK2 inhibitors and better understand the binding requirements of the ATP competitive inhibitors.
Sections du résumé
BACKGROUND
BACKGROUND
Casein Kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase with broad spectrum of substrates. This enzyme is widely expressed in eukaryotic cells and is overexpressed in different human cancers. Thus, the inhibition of CK2 can induce the physiological process of apoptosis leading to tumor cell death.
OBJECTIVES
OBJECTIVE
Selecting natural inhibitors toward the target enzyme using database mining.
METHODS
METHODS
With our continuous effort to discover new compounds with CK2 inhibitory effect, several commercial natural databases were searched using molecular modeling approach and the selected compounds were evaluated in vitro.
RESULTS
RESULTS
Three compounds were selected as candidates and evaluated in vitro using CK2 holoenzyme, their effect on three cancer cell lines was determined. The selected candidates were weak inhibitors toward the target enzyme, only one compound showed moderate effect on cell viability.
CONCLUSION
CONCLUSIONS
Several natural databases were screened, compounds were selected and tested in vitro. Despite the unexpected low inhibitory activity of the tested compounds, this study can help in directing the search of potent CK2 inhibitors and better understand the binding requirements of the ATP competitive inhibitors.
Identifiants
pubmed: 32160849
pii: CAD-EPUB-105160
doi: 10.2174/1573409916666200311150744
doi:
Substances chimiques
Biological Products
0
Protein Kinase Inhibitors
0
Casein Kinase II
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
323-331Informations de copyright
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