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Synthesis and antiproliferative activity of 1-1,2,3-triazole-4-chromene--glucose hybrid compounds with dual inhibitory activity against EGFR/VEGFR-2 and molecular docking studies
Ist Teil von
New journal of chemistry, 2022-12, Vol.46 (48), p.23179-23197
Erscheinungsjahr
2022
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
A series of 1
H
-1,2,3-triazole-4
H
-chromene-
d
-glucose hybrid compounds
7a-o
was synthesized
via
click chemistry using 2-amino-7-propargyloxy-4
H
-chromene-3-carbonitriles
5a-o
and peracetylated
d
-glucopyranosyl azide, respectively. CuNP@montmorillonite K10 was used as the catalyst in the presence of DIPEA. All the synthesized 1
H
-1,2,3-triazoles exhibited potent anticancer activity
in vitro
against the tested cancer cells, including MCF-7, HepG2, and HeLa. Almost all these compounds had low cytotoxicity against WI-37 cells. Amongst the tested compounds, some compounds exhibited strong activity against the tested cancer cell lines with IC
50
< 5 μM, such as
7g
,
7m
, and
7o
against HepG2,
7b
,
7f
,
7g
, and
7k
against MCF-7,
7c
,
7e
, and
7n
against HeLa, and
7b
,
7j
, and
7n
against SK-LU-1 cancer cell lines. Compounds,
7b
,
7f
,
7g
, and
7k
, exhibited remarkable dual inhibitory activity against EGFR and VEGFR-2 tyrosine kinases in comparison with erlotinib and sorafenib, respectively. The resulted docking studies showed that the representative compound
7g
displayed a similar binding mode to erlotinib in the EGFR enzyme
4HJO
and showed good binding energies. Induced-fit docking and MM-GBSA calculations were carried out to elucidate the inhibitory potential of compound
7g
against the tested enzyme
4HJO
. The docking analysis showed that between the hydrophilic and hydrophobic interactions at the active site of the EGFR enzyme, the hydrogen-bond binding between the acetate functional group and appropriate amino acid residues displayed the most important contribution in intensifying the potency against this enzyme. The interaction of the Cys773 residue was the decisive interaction for the ligands to reside in the receptor of
4HJO
, and therefore the activity of the selected inhibitor. Further, 300 ns MD simulation of the
7g
/
4HJO
complex showed the stability of the ligand-protein complex and structural insights into its binding mode.
1
H
-1,2,3-Triazole-4
H
-chromene-
d
-glucose hybrids were synthesized and screened for their anticancer activity
in vitro
against MCF-7, HepG2, HeLa and WI-38 cells, and several had dual inhibitions against EGFR/VEGFR-2. IFD, MM-GBSA and MD simulations were also carried out.
Sprache
–
Identifikatoren
ISSN: 1144-0546
eISSN: 1369-9261
DOI: 10.1039/d2nj04373d
Titel-ID: cdi_rsc_primary_d2nj04373d
Format
–
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