Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase.
Amino Acids
/ metabolism
Antineoplastic Agents
/ metabolism
Azoles
/ metabolism
Binding Sites
/ physiology
Humans
Hydrogen Bonding
Indazoles
/ metabolism
Ligands
Molecular Docking Simulation
/ methods
Molecular Dynamics Simulation
Protein Binding
/ physiology
Vascular Endothelial Growth Factor Receptor-2
/ metabolism
DFT calculations
PIEDA analysis
VEGFR2 kinase
azoles
docking
hydrogen bond
kinases
molecular dynamics
semi-empirical calculations
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
07 Jul 2020
07 Jul 2020
Historique:
received:
26
05
2020
revised:
28
06
2020
accepted:
03
07
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
18
2
2021
Statut:
epublish
Résumé
Vascular endothelial growth factor receptor 2 (VEGFR2) is a key receptor in the angiogenesis process. The VEGFR2 expression is upregulated in many cancers so this receptor is an important target for anticancer agents. In the present paper, we analyse interactions of several dimeric indazoles, previously investigated for anticancer activity, with the amino acids present in the VEGFR2 binding pocket. Using the docking method and MD simulations as well as theoretical computations (SAPT0, PIEDA, semi-empirical PM7), we confirmed that these azoles can efficiently bind into the kinase pocket and their poses can be stabilised by the formation of hydrogen bonds, π-π stacking, π-cation, and hybrid interactions with some amino acids of the kinase cavity like Ala866, Lys868, Glu885, Thr916, Glu917, and Phe918.
Identifiants
pubmed: 32645858
pii: ijms21134793
doi: 10.3390/ijms21134793
pmc: PMC7369845
pii:
doi:
Substances chimiques
Amino Acids
0
Antineoplastic Agents
0
Azoles
0
Indazoles
0
Ligands
0
KDR protein, human
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
ID : 502-14-33084170-67213/2018
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