In Vitro and In Vivo Investigations into the Potential of Quinazoline and Quinoline Derivatives as NorA Efflux Pump Inhibitors Against Resistant Staphylococcus aureus Strains
Antibiotics,
Journal Year:
2025,
Volume and Issue:
14(4), P. 339 - 339
Published: March 26, 2025
Background:
Staphylococcus
aureus
is
a
highly
lethal
Gram-positive
bacterium
that
responsible
for
over
one
million
deaths
annually.
As
member
of
the
ESKAPE
pathogens,
its
methicillin-resistant
strains
(MRSA)
are
prevalent
worldwide
and
exhibit
significant
antimicrobial
resistance
(AMR).
Bacterial
efflux
pumps
play
pivotal
role
in
development
AMR
by
facilitating
expulsion
range
agents.
Methods:
The
S.
strain
SA-1199B,
which
overexpresses
NorA
carries
GrlA
mutation,
was
utilized
to
comprehensively
profile
mechanism
compounds
PQQ16P
PQK4F.
To
assess
toxicity
genotoxicity
these
compounds,
RAW
macrophages,
HEK
293T,
HepG2
cell
lines
were
utilized.
Female
BALB/c
mice
vivo
synergism
EPIs
with
CPX,
Results:
pump
inhibitors
(EPIs),
PQK4F,
enhanced
efficacy
antibacterial
ciprofloxacin
(CPX)
against
resistant
strains.
involved
inhibition
pump,
without
compromising
bacterial
membrane
permeability,
ATP
levels,
or
mammalian
calcium
channels.
Moreover,
significantly
augmented
bactericidal
post-antibiotic
effects
elevating
mutation
prevention
concentration
manifesting
substantial
human
cells.
Furthermore,
reduced
invasiveness
indicating
virulence.
Notably,
CPX
observed
mouse
infection
model.
Conclusions:
This
study
provides
evidence
potential
employing
combination
counteract
AMR,
both
vitro
vivo.
Language: Английский
Metabolomic Profiling and In Vitro Evaluation of Cytotoxic, Genotoxic, and Antigenotoxic Effects of Staphylea pinnata L. Extract from Italian Flora
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(3), P. 385 - 385
Published: March 6, 2025
Staphylea
pinnata
L.,
(S.
pinnata),
has
long
been
recognized
in
Europe
as
both
a
wild
food
source
and
traditional
medicinal.
This
study
aimed
to
characterize
the
metabolomic
profile
of
leaf
extract
S.
assess
its
cytotoxic,
genotoxic,
antigenotoxic
effects
vitro
for
first
time.
The
methanolic
leaves
was
analyzed
using
Ultra-Performance
Liquid
Chromatography–High-Resolution
Mass
Spectrometry
(UPLC-HRMS).
To
evaluate
properties,
cytokinesis
block
micronucleus
assay
performed
on
Chinese
hamster
ovarian
K1
cells.
analysis
revealed
wide
variety
metabolites
extract,
with
B-type
procyanidins
prodelphinidins
being
most
abundant.
genotoxicity
varied
depending
concentration;
at
lowest
concentration
(75
μg/mL),
it
showed
no
genotoxic
exhibited
properties
by
reducing
frequency
micronuclei
induced
mitomycin
C.
However,
highest
(300
demonstrated
effects.
In
conclusion,
displayed
which
may
be
attributed
phytochemical
composition.
These
findings
highlight
complex
nature
plant’s
bioactive
compounds,
suggesting
potential
therapeutic
applications
careful
consideration
dosage.
Additional
research
is
necessary
understand
mechanisms
underlying
these
properties.
Language: Английский
Phytochemical Profile and In Vitro Cytotoxic, Genotoxic, and Antigenotoxic Evaluation of Cistus monspeliensis L. Leaf Extract
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(24), P. 13707 - 13707
Published: Dec. 22, 2024
Cistus
monspeliensis
L.
(C.
monspeliensis)
is
used
in
Italian
folk
medicine.
This
study
was
performed
to
determine
genotoxic
and
antigenotoxic
effects
of
C.
leaf
extract
against
mitomycin
C
(MMC)
using
an
vitro
cytokinesis-block
micronucleus
assay
(CBMN)
the
Chinese
Hamster
Ovarian
K1
(CHO-K1)
cell
line.
The
phytochemical
composition
evaluated
untargeted
metabolomic
approach
by
employing
UPLC-PDA-ESI/MS.
automated
CBMN
carried
out
image
analysis
systems
with
a
widefield
fluorescence
microscope
ImageStreamX
imaging
flow
cytometer.
profile
showed,
as
most
abundant
metabolites,
punicalagin,
myricetin,
gallocathechin,
labdane-type
diterpene.
monspeliensis,
at
tested
concentrations
50,
100,
200
μg/mL,
did
not
induce
significant
micronuclei
frequency,
thus
indicating
absence
potential.
When
testing
for
antigenotoxicity
presence
MMC,
we
observed
hormetic
concentration-dependent
effect,
where
low
resulted
protective
effect
MMC-induced
higher
no
effect.
In
conclusion,
our
findings
demonstrate
that
and,
concentration,
exhibits
relation
this
final
point,
may
act
potential
chemo-preventive
agents.
Language: Английский