Chemistry & Biodiversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 11, 2024
Abstract
This
study
explores
new
anti‐inflammatory
agents
by
synthesizing
pyrazoline‐pyridine
hybrids
with
N‐butylsulfonated
covalent
organic
framework
(COF‐SO
3
H)
as
a
recyclable
catalyst,
achieving
excellent
yields
in
just
one
minute.
The
protocol
was
successfully
scaled
up
to
multi‐gram
scale,
highlighting
its
robustness
and
efficiency,
it
operates
without
the
need
for
column
chromatography.
Among
synthesized
hybrids,
compound
5d
,
hybrid
bearing
an
indole
moiety,
emerged
potent
antioxidant
agent.
It
effectively
inhibited
PDE4B
activation
IC
50
value
of
99.38
nM,
adversely
affecting
HEK
cells.
Compound
demonstrated
dual
activity
significantly
reducing
ROS
production
restoring
mitochondrial
health
LPS‐stimulated
A549
cells,
while
also
downregulating
IL‐1β
NF‐ĸB/p65
expression
In
silico
studies
confirmed
’s
strong
binding
PDE4B,
stable
RMSD
RMSF
values,
indicating
potential
effective
inhibitor.
exhibited
favorable
physicochemical
properties,
met
drug‐likeness
criteria,
showed
low
toxicity
predicted
silico.
These
findings
suggest
that
has
significant
therapeutic
agent
inflammatory
diseases
due
activities.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(8), С. 7336 - 7336
Опубликована: Апрель 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,
Год журнала:
2024,
Номер
8, С. 100482 - 100482
Опубликована: Янв. 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.
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,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 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.
