Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2021,
Номер
36(1), С. 1732 - 1750
Опубликована: Янв. 1, 2021
There
is
an
urgent
need
to
design
new
anticancer
agents
that
can
prevent
cancer
cell
proliferation
even
with
minimal
side
effects.
Accordingly,
two
series
of
3-methylquinoxalin-2(1H)-one
and
3-methylquinoxaline-2-thiol
derivatives
were
designed
act
as
VEGFR-2
inhibitors.
The
synthesised
evaluated
in
vitro
cytotoxic
against
human
lines
namely,
HepG-2
MCF-7.
Also,
the
assessed
for
their
VEGFR-2inhibitory
effect.
most
promising
member
11e
further
investigated
reach
a
valuable
insight
about
its
apoptotic
effect
through
cycle
apoptosis
analyses.
Moreover,
deep
investigations
carried
out
compound
using
western-plot
analyses
detect
some
parameters
including
caspase-9,
caspase-3,
BAX,
Bcl-2.
Many
silico
docking,
ADMET,
toxicity
studies
performed
predict
binding
affinity,
pharmacokinetic,
drug
likeness,
compounds.
results
revealed
compounds
11e,
11g,
12e,
12g,
12k
exhibited
activities
(IC50
range
2.1
−
9.8
µM),
comparing
sorafenib
=
3.4
2.2
µM
MCF-7
HepG2,
respectively).
11b,
11f,
12f,
showed
highest
inhibitory
2.9
5.4
3.07
nM).
Additionally,
had
good
potential
arrest
HepG2
growth
at
G2/M
phase
induce
by
49.14%
compared
control
cells
(9.71%).
As
well,
such
significant
increase
level
caspase-3
(2.34-fold),
caspase-9
BAX
(3.14-fold),
decrease
Bcl-2
(3.13-fold).
For
studies,
mode
similar
reference
(sorafenib).
RSC Medicinal Chemistry,
Год журнала:
2023,
Номер
15(1), С. 10 - 54
Опубликована: Окт. 20, 2023
Many
researchers
around
the
world
are
working
on
development
of
novel
anticancer
drugs
with
different
mechanisms
action.
In
this
case,
coumarin
is
a
highly
promising
pharmacophore
for
drugs.
Besides,
hybridization
moiety
other
pharmacophores
has
emerged
as
potent
breakthrough
in
treatment
cancer
to
decrease
its
side
effects
and
increase
efficiency.
This
review
aims
provide
comprehensive
overview
recent
derivatives
their
application
Herein,
we
highlight
describe
largest
number
research
works
reported
field
from
2015
August
2023,
along
action
structure-activity
relationship
studies,
making
articles
published
topic
date.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2020,
Номер
35(1), С. 831 - 839
Опубликована: Янв. 1, 2020
In
the
current
medical
era,
spirooxindole
motif
stands
out
as
a
privileged
heterospirocyclic
scaffold
that
represents
core
for
wide
range
of
bioactive
naturally
isolated
products
(such
Strychnofoline
and
spirotryprostatins
A
B)
synthetic
compounds.
Interestingly,
no
much
attention
has
been
paid
to
develop
derivatives
with
dual
antioxidant
anticancer
activities.
this
context,
series
spirooxindoles
6a-p
was
examined
their
effect
towards
HepG2
hepatocellular
carcinoma
PC-3
prostate
cancer
cell
lines.
Spirooxindole
6a
found
be
an
efficient
anti-proliferative
agent
both
cells
(IC50
=
6.9
11.8
µM,
respectively).
Afterwards,
assessed
its
apoptosis
induction
potential
in
cells,
where
pro-apoptotic
impact
approved
via
significant
elevation
Bax/Bcl-2
ratio
expression
levels
caspase-3,
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2019,
Номер
34(1), С. 322 - 332
Опубликована: Янв. 1, 2019
In
connection
with
our
research
program
on
the
development
of
novel
anticancer
candidates,
herein
we
report
design
and
synthesis
series
1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas
5a–l.
The
target
pyridins
were
evaluated
for
their
in
vitro
activity
against
two
cancer
cell
lines:
non-small
lung
A549
line
colon
HCT-116
line.
Compound
5l
emerged
as
most
active
congener
towards
both
lines
IC50
values
equal
to
3.22
±
0.2
2.71
0.16
µM,
respectively,
which
are
comparable
those
Doxorubicin;
2.93
0.28
3.10
0.22,
respectively.
Furthermore,
compound
stood
out
potent
pyridine
derivative
(mean
%
GI
=
40),
at
US-NCI
Developmental
Therapeutic
Program
assay,
broad-spectrum
antitumor
tested
from
all
subpanels.
was
able
provoke
apoptosis
cells
evidenced
by
decreased
expression
anti-apoptotic
Bcl-2
protein,
enhanced
pro-apoptotic
proteins
levels;
Bax,
cytochrome
C,
p53,
caspase-3
caspase-9.
Moreover,
disrupted
cycle
via
alteration
Sub-G1
phase
arresting
G2-M
stage.
Also,
showed
a
significant
increase
percent
annexinV-FITC
positive
apoptotic
1.99
15.76%.
