Toxicology Mechanisms and Methods,
Год журнала:
2024,
Номер
unknown, С. 1 - 11
Опубликована: Июль 30, 2024
The
SH-SY5Y
human
neuroblastoma
cell
line
is
a
standard
in
vitro
experimental
model
of
neuronal-like
cells
used
neuroscience
and
toxicological
research.
These
can
be
differentiated
into
mature
neurons,
most
commonly
using
retinoic
acid
(RA).
Despite
differences
characteristics,
both
undifferentiated
are
However,
due
to
uncertainties
regarding
the
expression
specific
markers
neural
function
each
culture,
there
no
definite
conclusion
on
which
culture
better
suited
for
(neuro)toxicological
and/or
investigations.
To
address
this
dilemma,
we
investigated
basal
expression/activity
key
elements
acetylcholine,
dopamine,
serotonin,
GABA
neurotransmitter
pathways,
along
with
involved
exocytosis
neurotransmitters,
neuron
electrophysiological
activity
RA-differentiated
six-day
differentiation
protocol.
Our
findings
revealed
that
types
functionally
active.
While
exhibited
greater
multipotency
tested
markers,
those
expressed
showed
higher
levels
cells.
results
suggest
protocol
RA
induces
maturation,
but
not
phenotype.
expression,
together
their
sensitivity
xenobiotic
exposure
more
simple
cultivation
protocols,
make
them
candidate
high
throughput
screenings.
Differentiated
neurons
researches
require
Molecules,
Год журнала:
2023,
Номер
28(3), С. 978 - 978
Опубликована: Янв. 18, 2023
Quinazolines
are
nitrogen-containing
heterocycles
that
consist
of
a
benzene
ring
fused
with
pyrimidine
ring.
Quinazolinones,
oxidized
quinazolines,
promising
compounds
wide
range
biological
activities.
In
the
pharmaceutical
field,
quinazolinones
building
blocks
more
than
150
naturally
occurring
alkaloids
isolated
from
different
plants,
microorganisms,
and
animals.
Scientists
give
continuous
interest
in
this
moiety
due
to
their
stability
relatively
easy
methods
for
preparation.
Their
lipophilicity
is
another
reason
as
it
helps
penetration
through
blood–brain
barrier
which
makes
them
suitable
targeting
central
nervous
system
diseases.
Various
modifications
substitutions
around
quinazolinone
changed
activity
significantly
changes
physicochemical
properties.
Structure–activity
relationship
(SAR)
studies
revealed
positions
2,
6,
8
systems
significant
pharmacological
addition,
has
been
suggested
addition
heterocyclic
moieties
at
position
3
could
increase
activity.
review,
we
will
highlight
chemical
properties
quinazolinones,
including
reactions
Moreover,
try
modify
some
old
SAR
according
updated
activities
last
twelve
years.
Archiv der Pharmazie,
Год журнала:
2023,
Номер
356(11)
Опубликована: Сен. 21, 2023
In
this
study,
new
quinazoline-chromene
hybrid
compounds
were
synthesized.
The
cytotoxic
effects
on
cell
viability
of
the
tested
against
A549
human
lung
adenocarcinoma
and
BEAS-2B
healthy
bronchial
epithelial
lines
in
vitro.
addition,
ability
active
to
inhibit
migration
was
tested.
Molecular
docking
studies
performed
evaluate
ligand-protein
interactions,
molecular
dynamics
simulations
determine
interactions
stability
complexes.
silico
absorption,
distribution,
metabolism,
excretion
(ADME)
conducted
estimate
drug-likeness
compounds.
Compounds
4
(IC50
=
51.2
µM)
5
44.2
found
be
most
agents
cells.
They
are
more
selective
cells
than
reference
drug
doxorubicin.
also
have
significantly
migration.
best
scores
epidermal
growth
factor
receptor
(EGFR)
(-11.300
-11.226
kcal/mol)
vascular
endothelial
2
(VEGFR2)
(-10.987
-11.247
kcal/mol),
respectively.
MD
simulations,
strong
hydrogen
bond
above
80%
simulation
times
showed
a
low
ligand
root
mean
square
deviation
(RMSD)
around
Å.
According
ADME
analysis,
exhibit
excellent
pharmacokinetic
characteristics.
Chemistry & Biodiversity,
Год журнала:
2023,
Номер
20(9)
Опубликована: Авг. 19, 2023
Abstract
Herein,
new
derivatives
of
α
,
β‐
unsaturated
ketones
based
on
oleanolic
acid
(
4
a
–
i
)
were
designed,
synthesized,
characterized,
and
tested
against
human
prostate
cancer
(PC3).
According
to
the
in
vitro
cytotoxic
study,
title
compounds
showed
significantly
lower
toxicity
toward
healthy
cells
(HUVEC)
comparison
with
reference
drug
doxorubicin.
The
lowest
IC
50
values
PC3
cell
lines
b
(7.785
μM),
c
(8.869
e
(8.765
μM).
results
ADME
calculations
that
drug‐likeness
parameters
within
defined
ranges
according
Lipinski's
Jorgensen's
rules.
For
most
potent
molecular
docking
analysis
using
induced
fit
(IFD)
protocol
was
performed
three
protein
targets
(PARP,
PI3K,
mTOR).
Based
IFD
scores,
compound
had
highest
calculated
affinity
for
PARP1,
while
higher
affinities
mTOR
PI3K.
MM‐GBSA
high
binding
formed
stable
complexes
targets.
Finally,
ns
dynamics
simulation
study
behavior
target
under
silico
physiological
conditions.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
42(7), С. 3441 - 3458
Опубликована: Май 26, 2023
AbstractAbstractThe
synthesis
and
biological
assessment
of
novel
multi-functionalized
pyrrolidine-containing
benzenesulfonamides
were
reported
along
with
their
antimicrobial,
antifungal,
CAs
inhibition,
AChE
inhibition
as
well
DNA-binding
effects.
The
chemical
structure
the
compounds
was
elucidated
by
using
FTIR,
NMR,
HRMS.
Compound
3b,
which
had
Ki
values
17.61
±
3.58
nM
(hCA
I)
5.14
0.61
II),
found
be
most
potent
inhibitor.
Compounds
6a
6b
showed
remarkable
effects
22.34
4.53
27.21
3.96
in
comparison
to
tacrine.
6a–6c
moderate
antituberculosis
effect
on
M.
tuberculosis
a
MIC
value
15.62
μg/ml.
weaker
antifungal
antibacterial
activity
range
500–62.5
μg/ml
against
standard
bacterial
fungal
strains.
Besides
these
above,
molecular
docking
studies
performed
examine
evaluate
interaction
(3b,
6b)
current
enzymes
(CAs
AChE).
Novel
gained
interest
terms
enzyme
inhibitory
potencies.
Therefore,
inhibitors
may
considered
lead
modified
for
further
research.Communicated
Ramaswamy
H.
SarmaKeywords:
Acetylcholinesteraseantimicrobialbenzenesulfonamidecarbonic
anhydrasemolecular
dockingpyrazolepyrrolidines
Disclosure
statementNo
potential
conflict
author(s).Additional
informationFundingWe
gratefully
acknowledge
financial
support
from
Çukurova
University
(Projects
No:
TSA-2021-13814
TSA-2021-13443).Correction
StatementThis
article
has
been
corrected
minor
changes.
These
changes
do
not
impact
academic
content
article.
