ChemistrySelect,
Journal Year:
2024,
Volume and Issue:
9(46)
Published: Dec. 1, 2024
Abstract
We
synthesized
a
novel
compound
library
featuring
spirooxindole
core
structure
combined
with
various
heterocycles,
including
benzofuran,
benzothiophene,
and
thiophene
scaffolds.
Evaluation
using
MTT
assays
against
HepG2,
4T1,
MDA‐MB‐231
cells
revealed
the
most
potent
candidate,
hybrid
5c
,
an
IC50
of
5
±
0.6
µM
inducing
G2/M
phase
cell
cycle
arrest,
inhibition
wound
healing,
induction
ROS.
Selected
conjugates
exhibited
significant
inhibitory
potential
MDM2,
KD
values
ranging
from
0.0531
to
16.8
µM.
Notably,
salt
analogue
5q
demonstrated
highest
activity
at
K
D
=
53.1
nM.
Molecular
docking
studies
excellent
accommodation
designed
compounds
within
MDM2
receptor.
All
displayed
favorable
ADME
profiles,
suggesting
their
as
lead
for
further
optimization.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(8), P. 7336 - 7336
Published: April 15, 2023
A
highly
stereo-selective,
one-pot,
multicomponent
method
was
chosen
to
synthesize
the
novel
functionalized
1,
3-cycloaddition
spirooxindoles
(SOXs)
(4a-4h).
Synthesized
SOXs
were
analyzed
for
their
drug-likeness
and
ADME
parameters
screened
anticancer
activity.
Our
molecular
docking
analysis
revealed
that
among
all
derivatives
of
(4a-4h),
4a
has
a
substantial
binding
affinity
(∆G)
-6.65,
-6.55,
-8.73,
-7.27
Kcal/mol
with
CD-44,
EGFR,
AKR1D1,
HER-2,
respectively.
functional
study
demonstrated
SOX
impact
on
human
cancer
cell
phenotypes
exhibiting
abnormality
in
cytoplasmic
nuclear
architecture
as
well
granule
formation
leading
death.
treatment
robustly
induced
reactive
oxygen
species
(ROS)
generation
cells
observed
by
enhanced
DCFH-DA
signals.
Overall,
our
results
suggest
(4a)
targets
HER-2
induces
ROS
cells.
We
conclude
could
be
explored
potential
chemotherapeutic
molecule
against
various
cancers
appropriate
pre-clinical
vitro
vivo
model
systems.
Chemical Physics Impact,
Journal Year:
2024,
Volume and Issue:
8, P. 100482 - 100482
Published: Jan. 22, 2024
The
published
molecule
(S)-3-Benzyl-5-(phenylselanyl)-6-(p-tolyl)-3,4-dihydropyran-2-one
(3B6PL)
was
selected
for
the
identification
of
anticancer
properties,
and
computational
calculations
were
employed
using
density
function
theory
(DFT)
with
B3LYP/6-311++G
(d,p)
basis
set
to
validate
proposed
molecular
structure
features
by
theoretical
calculations.
Herein,
FT-IR,
UV-800,
1H
NMR,
13C
NMR
analytical
techniques
used
characterization
molecule.
In
characteristic
frequencies
compared
an
appropriate
scaling
factor
(0.961)
potential
energy
distribution
(PED)
simulated
spectra
3B6PL.
Moreover,
UV-800
spectral
data
validated
NBO
that
demonstrated
charge
transfer
in
molecules
exhibits
a
prominent
second-order
perturbation
energy,
E(2)
value
is
309.85
kcal/mol.
HOMO-LUMO,
Molecular
electrostatic
(MEP)
both
find
molecule's
electrical
as
well
its
softness,
hardness,
overall
stability.
To
understand
reactive
locations
molecule,
fukui
functions
have
been
employed.
exceptional
NLO
(non-linear
optical)
characteristics
demonstrated,
intermolecular
interactions
evaluated
Hirshfeld
surface
well.
On
contrary,
druglikeness
under
Lipinski's
rule
five
ADME/T
studies.
In-silico
analysis
docking
also
against
kinase
insert
domain
receptors
VEGFR
showed
binding
affinities
-6.3
kcal/mol
VEGFR-ligand
complex
preliminary
investigation.
Therefore,
this
compound
could
be
in-vitro
in-vivo
analyses
out
cytotoxicity
derivatized
enhance
potent
properties.
ChemistrySelect,
Journal Year:
2024,
Volume and Issue:
9(4)
Published: Jan. 24, 2024
Abstract
p38
MAP
kinases
are
involved
in
numerous
inflammatory
diseases.
A
series
of
14
molecules
1,2,3
triazole
linked
4‐((2‐cyclohexyl‐4,5‐diphenyl‐1
H
‐imidazol‐1‐yl)
methyl)‐1‐phenyl
hybrids(7
a–7
n)
has
been
synthesized
by
click
reaction.
Spectral
data
characterized
all
the
compounds.
The
final
compounds
were
screened
for
vitro
kinase
inhibitory
activity.
Three
from
7
c,
f,
and
n
expounded
superior
activity
with
IC
50
values
234.08±19.65
nM,
222.68±20.69
241.70±20.51
nM
respectively
while
two
(7
d
e)
showed
considerable
compared
to
prototype
drug
Adezmapimod
(SB203580)
(IC
value
257.13±23.94
nM).
docking
study
revealed
that
three
f,7
g,
higher
binding
affinities
than
Adezmapimod.
“Desmond
v3.6
Program”
was
utilized
conduct
MD
simulations.
result
compound
f
conformationally
stable.
ADME
studies
performed
using
Swiss
algorithm.
Studies
compound‘s
defiance
Lipinski's
rule
is
within
acceptable
ranges
few
violations.
Compound
orally
active
good
gastrointestinal
absorption
range.
search
newer
increased
resulted
identifying
a
novel
subclass
inhibitors.
Expert Opinion on Therapeutic Patents,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 14, 2025
P2Y12
receptor
(P2Y12R)
is
a
G
protein-coupled
that
plays
crucial
role
in
regulating
platelet
activation
and
aggregation.
P2Y12R
involved
various
processes
such
as
renal
fibrosis,
cancer,
ischemic
disease,
related
complications,
making
it
an
appealing
target
for
therapeutic
interventions.
Over
the
past
decade,
discovery
development
of
antagonists
have
significantly
advanced,
offering
novel
treatment
options
improve
clinical
outcomes.
This
review
covers
reported
patents
issued
online
databases
World
Intellectual
Property
Organization
European
Patent
Office
from
2019
to
2024.
introduces
existing
evaluates
potential
these
compounds.
Reversible
offer
potentially
safer
alternative
currently
dominant
irreversible
on
market,
they
allow
more
controlled
inhibition
can
reduce
toxicity
adverse
effects
associated
with
conventional
drugs.
Importantly,
integration
computational
drug
design
molecular
docking
studies
optimization
represents
significant
advancement
precision
medicine.
not
only
provides
valuable
structural
scaffolds
but
also
stimulates
ideas
developing
promising
drugs
are
both
safe
efficacious.
