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,
Organic Letters,
Год журнала:
2019,
Номер
21(4), С. 926 - 930
Опубликована: Фев. 4, 2019
A
novel
strategy
for
the
construction
of
2,2-diacyl
spirocyclohexanones
3
has
been
demonstrated
on
basis
an
NHC-catalyzed
[3C
+
3C]
annulation
potassium
2-oxo-3-enoates
with
2-ethylidene
1,3-indandiones.
Furthermore,
enantioenriched
was
obtained
in
good
to
excellent
yields
enantioselectivities
when
chiral
N-heterocyclic
carbene
(NHC)
employed.
Notably,
ring
opening
resulting
hydrazine
led
formation
phthalazinones
yields.
Drug Design Development and Therapy,
Год журнала:
2020,
Номер
Volume 14, С. 497 - 508
Опубликована: Фев. 1, 2020
Introduction:
Histone
deacetylases
(HDACs)
represent
one
of
the
most
validated
cancer
targets.
The
inhibition
HDACs
has
been
proven
to
be
a
successful
strategy
for
development
novel
anticancer
candidates.
Methods:
This
work
describes
design
and
synthesis
new
set
HDAC
inhibitors
(
7a-c
8a,
b
)
utilizing
ligustrazine
as
cap
moiety,
achieving
pharmacophoric
features
required
induce
desired
inhibition.
Results:
newly
synthesized
derivatives
were
evaluated
their
potential
inhibitory
activity
toward
two
class
I
histone
deacetylases,
namely
HDAC1
HDAC2.
tested
ligustrazine-based
compounds
more
potent
HDAC2
(IC
50
range:
53.7–
205.4
nM)
than
114.3–
2434.7
nM).
Furthermore,
antiproliferative
activities
against
HDAC-expressing
cell
lines;
HT-29
SH-SY5Y
examined
by
MTT
assay.
Moreover,
molecular
docking
study
designed
8a,b
was
carried
out
investigate
binding
pattern
within
prospective
targets;
(PDB-ID:
4BKX)
6G3O).
Discussion:
Compound
7a
found
analog
in
this
with
IC
values
equal
114.3
53.7
nM,
respectively.
it
effective
counterpart
=
1.60
μM),
4.7-fold
enhanced
efficiency
reference
drug
Gefitinib
7.63
μM)
cells.
Whereas,
compound
8a
1.96
active
member
cells,
being
2.5-times
4.99
μM).
Collectively,
these
results
suggest
that
merits
further
optimization
an
HDACI
lead
compound.
Keywords:
Inhibitors,
Ligustrazine,
Anticancer
agents,
In
silico
study,
Synthesis
ACS Applied Bio Materials,
Год журнала:
2022,
Номер
5(11), С. 5333 - 5346
Опубликована: Окт. 26, 2022
Photothermal/photodynamic
therapies
(PTT/PDT)
are
multimodal
approaches
employing
near-infrared
(NIR)
light-responsive
photosensitizers
for
cancer
treatment.
In
the
current
study,
IR-775,
a
hydrophobic
photosensitizer,
was
used
in
combination
with
polyphenols
(p)-rich
ethyl
acetate
extract
from
Terminalia
chebula
to
treat
cancer.
IR-775
dye
and
were
encapsulated
poly(lactic
acid)
polymeric
nanosystem
(PpIR
NPs)
increase
cell
bioavailability.
The
hydrodynamic
diameter
of
PpIR
NPs
is
142.6
±
2
nm
exhibited
physical
stability.
showed
enhanced
cellular
uptake
lung
line
(A549).
Cell
cytotoxicity
results
indicate
that
more
than
82.46
3%
death
upon
NIR
light
treatment
compared
control
groups.
Both
PDT
PTT
generate
reactive
oxygen
species
(ROS)
cause
hyperthermia,
thereby
enhancing
death.
Qualitative
quantitative
analyses
have
depicted
irradiation
decreased
protein
expression
HSP70
PARP,
increased
γ-H2AX,
which
collectively
lead
After
irradiation,
relative
gene
patterns
CDK2Na
also
downregulated.
Further,
has
been
studied
3D
cells
ovo
bioimaging
zebrafish
models.
conclusion,
show
good
present
potential
bioimaging.
Journal of Medicinal Chemistry,
Год журнала:
2022,
Номер
65(24), С. 16099 - 16127
Опубликована: Дек. 13, 2022
The
nuclear
enzymes
called
poly(ADP-ribose)polymerases
(PARPs)
are
known
to
catalyze
the
process
of
PARylation,
which
plays
a
vital
role
in
various
cellular
functions.
They
have
become
important
targets
for
discovery
novel
antitumor
drugs
since
their
inhibition
can
induce
significant
lethality
tumor
cells.
Therefore,
researchers
all
over
world
been
focusing
on
developing
and
potent
PARP
inhibitors
cancer
therapy.
Studies
shown
that
other
agents,
such
as
EZH2
EGFR
inhibitors,
play
synergistic
combined
with
effects
may
provide
rational
strategy
improve
effectiveness
current
anticancer
regimens.
In
this
Perspective,
we
sum
up
recent
advance
PARP-targeted
including
single-target
inhibitors/degraders
dual-target
inhibitors/degraders,
discuss
fundamental
theory
these
give
insight
into
corresponding
structure–activity
relationships
agents.
