Research Square (Research Square),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Oct. 17, 2022
Abstract
Intracerebral
hemorrhage
(ICH)
is
a
devasting
stroke
type
with
high
mortality
and
disability.
Inflammatory
response
induced
by
macrophages/microglia
(M/Ms)
activation
one
of
the
leading
causes
brain
damage
after
ICH.
The
anti-inflammatory
effects
resveratrol
(RSV)
have
already
been
evaluated
in
several
models
central
nervous
system
disease.
Therefore,
we
designed
current
study
to
assess
role
RSV
ICH
explore
its
downstream
mechanism
related
Sirt3.
autologous
artery
blood
injection
was
administrated
create
an
mouse
model.
M/Ms
specific
Sirt3
knockout
f/f
;
CX3CR1-Cre
(Sirt3
cKO)
used
evaluate
on
treatment.
Neuronal
function
hematoma
volume
were
assessed
indicate
damage.
pro-inflammatory
marker
(CD16)
cytokine
(TNF-α)
measured
inflammatory
effects.
Our
results
showed
that
treatment
alleviates
neurological
deficits,
reduces
apoptosis,
increases
clearance
day
7
In
addition,
effectively
suppressed
CD16
+
decreased
TNF-α
release.
cKO
mice,
protective
abolished,
indicating
potential
partially
due
signaling
activation.
could
be
promising
candidate
therapeutic
agent
for
target
inhibit
inflammation.
European Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
248, P. 115091 - 115091
Published: Jan. 7, 2023
Psychiatric
and
neurological
disorders
affect
millions
of
people
worldwide.
Currently
available
treatments
may
help
to
improve
symptoms,
but
they
cannot
cure
the
diseases.
Therefore,
there
is
an
urgent
need
for
potent
safe
therapeutic
solutions.
8-Amide
8-carbamatecoumarins
were
synthetized
evaluated
as
human
monoamine
oxidase
A
B
(hMAO-A
hMAO-B)
inhibitors.
Comparison
between
both
scaffolds
has
been
established,
we
hypothesized
that
introduction
different
substituents
can
modulate
hMAO
activity
selectivity.
N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide
(9)
ethyl
N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate
(20)
proved
be
most
active
selective
hMAO-A
inhibitors
(IC50
=
15.0
nM
IC50
22.0
nM,
respectively),
being
compound
9
irreversible
inhibitor
twenty-four
times
more
in
vitro
than
moclobemide,
a
drug
used
treatment
depression
anxiety.
Based
on
PAMPA
assay
results,
compounds
good
candidates
cross
blood-brain
barrier.
In
addition,
these
showed
non-significant
cytotoxicity
neuronal
viability
assays.
Also,
best
have
t1/2
6.84
min,
intrinsic
clearance
195.63
μL
min-1
mg-1
protein,
chemically
stable
at
pH
3.0,
7.4
10.0.
Docking
studies
performed
better
understand
binding
affinities
selectivity
profiles
isoforms.
Finally,
theoretical
drug-like
properties
calculations
corroborate
potential
search
new
solutions
psychiatric
depression.
European Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
277, P. 116763 - 116763
Published: Aug. 10, 2024
5-Methoxy-3-(5-methoxyindolin-2-yl)-1H-indole
(3),
whose
structure
was
unambiguously
elucidated
by
X-ray
analysis,
identified
as
a
multi-target
compound
with
potential
application
in
neurodegenerative
diseases.
It
is
low
nanomolar
inhibitor
of
QR2
(IC
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 24, 2024
Abstract
In
this
work
we
introduce
Target
Fisher,
a
consensus
structure‐based
target
prediction
tool
that
integrates
molecular
docking
and
machine
learning
with
the
aim
to
aid
in
identification
of
potential
biological
targets
optimization
use
bioassays.
Fisher
uses
per‐residue
energy
decomposition
profiles
extracted
from
poses
as
fingerprints
train
target‐specific
models.
It
provides
predictions
for
curated
set
37
protein
targets,
covering
diverse
range
entities,
offers
user‐friendly
interface
accessible
via
web
server
(
https://gqc.quimica.unlp.edu.ar/targetfisher/
).
sense,
is
valuable
organic
medicinal
chemistry
groups
identification,
drug
discovery
repurposing.
As
case
study,
demonstrate
efficacy
by
screening
small
library
assorted
natural
products
relevant
neurodegenerative
diseases,
which
resulted
experimental
validation
selective
inhibitors
monoamine
oxidase
B
(MAO−B).
IntechOpen eBooks,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 20, 2024
Phyto-nanoparticles
derived
from
plants
are
an
emerging
class
of
nanomaterials
that
integrate
the
versatility
nanotechnology
with
therapeutic
potential
botanical
ingredients.
This
chapter
explores
utility
phyto-nanoparticles
in
stimulating
osteogenesis
for
applications
bone
tissue
engineering
and
regeneration.
Plant
extracts
serve
as
sustainable
nanoparticle
building
blocks
or
coatings
through
green
synthesis
approaches.
Resultant
possess
multifunctional
capabilities
stemming
bioactive
phytochemical
components
enable
modulation
osteogenic
cells
like
mesenchymal
stem
osteoblasts.
Diverse
based
on
tea,
aloe
vera,
curcumin,
other
plant
derivatives
have
demonstrated
ability
to
enhance
osteoblast
differentiation,
proliferation,
mineralized
matrix
deposition.
Proposed
mechanisms
encompass
direct
cell
interactions,
sustained
intracellular
delivery
drugs,
complementary
anti-inflammatory
effects.
Capitalizing
these
properties,
researchers
designed
innovative
scaffolds,
functionalized
implants,
developed
carriers
diseases
osteoporosis
using
phyto-nanotechnology.
Further
innovations
fabrication
strategies
integration
technologies
will
realize
smarter,
personalized
plant-based
nanosystems
advance
regeneration
dramatically.
New Journal of Chemistry,
Journal Year:
2022,
Volume and Issue:
46(42), P. 20347 - 20353
Published: Jan. 1, 2022
An
efficient
and
eco-friendly
electrosynthesis
of
2-alkoxy/aryloxy-5-substituted
1,3,4-oxadiazoles,
5-substituted
1,3,4-oxadiazol-2(3
H
)-ones
has
been
developed
through
the
annulation
aldehydes
carbazates.
Food
compounds
and
their
molecular
interactions
are
crucial
for
health
provide
new
chemotypes
targets
drug
nutraceutic
design.
Here
we
retrieve
analyze
the
complete
set
of
published
food
with
human
proteins,
using
FooDB
as
compound
ChEMBL
source
interactions.
The
data
is
analyzed
in
terms
19
target
classes
classes,
showing
a
small
fraction
assignment
(1.6%)
unraveling
multiple
gaps
chemobiological
space
these
molecules.
By
well
established
cheminformatic
approaches
(Similarity
Ensemble
Approach
(SEA)
combined
maximum
Tanimoto
Coefficient
to
nearest
bioactive,
“SEA
+
TC”)
achieve
much
enhanced
(64.2%),
filling
many
hypothesis
fast
focused
testing.
publishing
datasets
analyses
expect
resources
speed
up
full
clarification
compounds,
opening
opportunities
Research Square (Research Square),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Oct. 17, 2022
Abstract
Intracerebral
hemorrhage
(ICH)
is
a
devasting
stroke
type
with
high
mortality
and
disability.
Inflammatory
response
induced
by
macrophages/microglia
(M/Ms)
activation
one
of
the
leading
causes
brain
damage
after
ICH.
The
anti-inflammatory
effects
resveratrol
(RSV)
have
already
been
evaluated
in
several
models
central
nervous
system
disease.
Therefore,
we
designed
current
study
to
assess
role
RSV
ICH
explore
its
downstream
mechanism
related
Sirt3.
autologous
artery
blood
injection
was
administrated
create
an
mouse
model.
M/Ms
specific
Sirt3
knockout
f/f
;
CX3CR1-Cre
(Sirt3
cKO)
used
evaluate
on
treatment.
Neuronal
function
hematoma
volume
were
assessed
indicate
damage.
pro-inflammatory
marker
(CD16)
cytokine
(TNF-α)
measured
inflammatory
effects.
Our
results
showed
that
treatment
alleviates
neurological
deficits,
reduces
apoptosis,
increases
clearance
day
7
In
addition,
effectively
suppressed
CD16
+
decreased
TNF-α
release.
cKO
mice,
protective
abolished,
indicating
potential
partially
due
signaling
activation.
could
be
promising
candidate
therapeutic
agent
for
target
inhibit
inflammation.
