Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2021,
Номер
36(1), С. 987 - 999
Опубликована: Янв. 1, 2021
As
one
of
the
most
lethal
malignancies,
lung
cancer
is
considered
to
account
for
approximately
one-fifth
all
malignant
tumours-related
deaths
worldwide.
This
study
reports
synthesis
and
in
vitro
biological
assessment
two
sets
3-methylbenzofurans
(4a–d,
6a–c,
8a–c
11)
3-(morpholinomethyl)benzofurans
(15a–c,
16a–b,
17a–b
18)
as
potential
anticancer
agents
towards
non-small
cell
carcinoma
A549
NCI-H23
lines,
with
VEGFR-2
inhibitory
activity.
The
target
benzofuran-based
derivatives
efficiently
inhibited
growth
both
lines
IC50
spanning
ranges
1.48–47.02
0.49–68.9
µM,
respectively.
three
active
benzofurans
(4b,
15a
16a)
were
further
investigated
their
effects
on
cycle
progression
apoptosis
(for
4b)
lines.
Furthermore,
4b,
16a
displayed
good
activity
equal
77.97,
132.5
45.4
nM,
Abstract
Presently,
humanity
is
confronted
with
a
range
of
diseases
that
have
high
death
rates,
especially
those
linked
to
cancerous
growths.
Several
enzymes
and
proteins
been
discovered
as
highly
attractive
targets
for
cancer
treatment.
The
PARP
family
consists
17
members
plays
crucial
role
in
repairing
DNA
damage,
which
enables
the
survival
cells.
PARP-1
and,
lesser
extent,
PARP-2
display
above
90%
activity
response
thereby
distinguishing
them
apart
from
other
family.
Elevated
levels
were
observed
many
types
tumor
cells,
such
breast,
lung,
ovarian,
prostate,
melanomas.
In
an
attempt
provide
future
guide
developing
selective
inhibitors
over
minimize
resulting
side
effects
inhibitors,
we
constructed
structure-based
virtual
screening
approach
(SBVS).
Firstly.
A
3D
pharmacophore
was
based
on
interaction
inhibitor
compound
IV
.
After
that,
database
nearly
450,000
phthalimide-containing
screened
through
validated
pharmacophore,
165
compounds
retrieved.
retrieved
docked
into
active
site
where
only
5
MWGS-1-5
achieved
favorable
docking
score
than
reference
(-16.8
Kcal/mol).
Redocking
five
should
excellent
selectivity
PARP-2,
MWGS-1
Further
endorsement
via
molecular
dynamics
has
proven
higher
affinity
towards
PARP-1-
RMSD
values
1.42
2.8
Å,
respectively.
Journal of Medicinal Chemistry,
Год журнала:
2019,
Номер
63(1), С. 321 - 333
Опубликована: Дек. 3, 2019
The
sweeteners
saccharin
(SAC)
and
acesulfame
K
(ACE)
recently
entered
the
topic
of
anticancer
human
carbonic
anhydrase
(CA,
EC
4.2.1.1)
inhibitors,
as
they
showed
to
selectively
inhibit
tumor-associated
CAs
IX/XII
over
ubiquitous
CAs.
A
drug
design
strategy
is
here
reported,
which
took
SAC
ACE
leads
produced
a
series
2H-benzo[e][1,2,4]thiadiazin-3(4H)-one-1,1-dioxides
(BTD).
Many
derivatives
greater
potency
(KIs-CA
IX
19.1–408.5
nM)
selectivity
(II/IX
SI
2–76)
than
103,
2400
nM;
II/IX-SI
56,
>4)
against
CA
off-target
isoforms.
thorough
X-ray
crystallographic
study
depicted
their
binding
mode
both
II
IX-mimic.
most
representative
BTDs
were
characterized
in
vitro
for
antitumor
activity
A549,
PC-3,
HCT-116
cancer
cell
lines
normoxia
hypoxia.
two
effective
compounds
assayed
effect
on
several
apoptosis
markers,
identifying
promising
development
new
drugs.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2021,
Номер
36(1), С. 987 - 999
Опубликована: Янв. 1, 2021
As
one
of
the
most
lethal
malignancies,
lung
cancer
is
considered
to
account
for
approximately
one-fifth
all
malignant
tumours-related
deaths
worldwide.
This
study
reports
synthesis
and
in
vitro
biological
assessment
two
sets
3-methylbenzofurans
(4a–d,
6a–c,
8a–c
11)
3-(morpholinomethyl)benzofurans
(15a–c,
16a–b,
17a–b
18)
as
potential
anticancer
agents
towards
non-small
cell
carcinoma
A549
NCI-H23
lines,
with
VEGFR-2
inhibitory
activity.
The
target
benzofuran-based
derivatives
efficiently
inhibited
growth
both
lines
IC50
spanning
ranges
1.48–47.02
0.49–68.9
µM,
respectively.
three
active
benzofurans
(4b,
15a
16a)
were
further
investigated
their
effects
on
cycle
progression
apoptosis
(for
4b)
lines.
Furthermore,
4b,
16a
displayed
good
activity
equal
77.97,
132.5
45.4
nM,
