Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: Nov. 20, 2023
Significant
advancements
have
been
made
in
the
domain
of
targeted
anticancer
therapy
for
management
malignancies
recent
times.
VEGFR-2
is
characterised
by
its
pivotal
involvement
angiogenesis
and
subsequent
mechanisms
that
promote
tumour
cells
survival.
Herein,
novel
N-arylmethyl-aniline/chalcone
hybrids
5a–5n
were
designed
synthesised
as
potential
inhibitors.
The
activity
was
evaluated
at
NCI-USA,
resulting
identification
10
remarkably
potent
molecules
5a–5j
further
subjected
to
five-dose
assays.
Thereafter,
they
explored
their
inhibitory
where
5e
5h
emerged
most
induced
apoptosis
with
cell
cycle
arrest
SubG0-G1
phase
within
HCT-116
cells.
Moreover,
impact
on
some
key
apoptotic
genes
assessed,
suggesting
caspase-dependent
apoptosis.
Furthermore,
molecular
docking
dynamics
simulations
conducted
explore
binding
modes
stability
protein–ligand
complexes.
Future Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
15(22), P. 2065 - 2086
Published: Nov. 1, 2023
Background:
VEGFR-2
is
a
key
regulator
of
cancer
cell
proliferation,
migration
and
angiogenesis.
Aim:
Development
thieno[2,3-d]pyrimidine
derivatives
as
potential
anti-cancer
agents
targeting
VEGFR-2.
Methods:
Seven
in
vitro
nine
silico
studies
were
conducted.
Results:
Compound
10d
demonstrated
strong
anticancer
potential,
boosting
apoptosis
based
on
inhibition.
It
arrested
the
S
phase
cycle
upregulated
apoptotic
factors.
Docking
molecular
dynamics
simulation
confirm
stability
VEGFR-2–10d
complex
suggest
that
these
compounds
have
good
binding
affinities
to
In
addition,
drug-likeness
was
confirmed.
Conclusion:
Thieno[2,3-d]pyrimidines,
particularly
compound
10d,
has
effects
may
contribute
development
new
therapies.
BMC Chemistry,
Journal Year:
2024,
Volume and Issue:
18(1)
Published: Oct. 24, 2024
Abstract
New
Series
of
N
-Manniche
bases
3,4
(a-c)
and
5,6
(a-b)
were
synthesized
through
the
reaction
benzaldehyde
amine
with
3-methyl-4-(aryldiazenyl)-1H-pyrazol-5-ol
derivatives
2(a-c),
they
fully
characterized
by
FT-IR,
(
1
H,
13
C)
NMR
data
in
addition
to
their
mass
spectra.
The
Structural
Activity
Relationship
target
compounds
examined
for
cytotoxicity.
Some
newly
showed
promising
antiproliferation
properties
when
tested
against
HepG2
cancer
cells.
Compounds
4a,
5a,
6b
potent
cytotoxicity
IC
50
values
4.4,
3.46
2.52
µM
compared
Sorafenib
(IC
=
2.051
µM)
Roscovitine
4.18
µM).
Furthermore,
safe
THLE2
cells
higher
values.
Compound
exhibited
dual
VEGFR2/CDK-2
inhibition
activities;
it
had
an
value
0.2
μM
VEGFR2
93.2%,
0.458
CDK-2
88.7%.
In
comparison
untreated
control
group
(0.95%),
5a
(38.32%)
(42.9%)
considerably
increased
cell
population
total
apoptosis.
addition,
arrested
at
G0-G1
S
phases,
respectively.
Molecular
docking
experiments
confirmed
virtual
binding
mechanism
most
active
drugs,
which
found
have
good
affinities
both
receptor
sites.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: Nov. 20, 2023
Significant
advancements
have
been
made
in
the
domain
of
targeted
anticancer
therapy
for
management
malignancies
recent
times.
VEGFR-2
is
characterised
by
its
pivotal
involvement
angiogenesis
and
subsequent
mechanisms
that
promote
tumour
cells
survival.
Herein,
novel
N-arylmethyl-aniline/chalcone
hybrids
5a–5n
were
designed
synthesised
as
potential
inhibitors.
The
activity
was
evaluated
at
NCI-USA,
resulting
identification
10
remarkably
potent
molecules
5a–5j
further
subjected
to
five-dose
assays.
Thereafter,
they
explored
their
inhibitory
where
5e
5h
emerged
most
induced
apoptosis
with
cell
cycle
arrest
SubG0-G1
phase
within
HCT-116
cells.
Moreover,
impact
on
some
key
apoptotic
genes
assessed,
suggesting
caspase-dependent
apoptosis.
Furthermore,
molecular
docking
dynamics
simulations
conducted
explore
binding
modes
stability
protein–ligand
complexes.
