Abstract
Multidrug
Resistance
(MDR)
can
be
considered
one
of
the
most
frightening
adaptation
types
in
bacteria,
fungi,
protozoa,
and
eukaryotic
cells.
It
allows
organisms
to
survive
attack
many
drugs
used
daily
basis.
This
forces
development
new
more
complex,
highly
specific
fight
diseases.
Given
high
usage
medicaments,
poor
variation
active
chemical
cores,
self‐medication,
appearance
MDR
is
frequent
each
time,
has
been
established
as
a
serious
medical
social
problem.
Over
years
it
possible
identification
several
genes
proteins
responsible
for
with
that
blockers
them
reach
reversion
try
avoid
global
These
mechanisms
also
have
observed
cancer
cells,
calcium
channel
successful
reversion,
maleimide
found
included
them.
In
this
review,
we
explore
particularly
tree
main
involved
chemoresistance,
MRP1
(encoded
by
ABCC1),
BCRP
ABCG2)
P‐gp
ABCB1).
The
participation
remarkably
important,
aspects
its
regulations
are
discussed.
Additionally,
address
history,
mechanisms,
efforts,
specifically
focused
on
synthesis
MDR‐reversers
co‐administration,
well
how
their
biological
applications
imperative
expand
available
information
very
plausible
source.
Journal of Inflammation Research,
Год журнала:
2024,
Номер
Volume 17, С. 1735 - 1763
Опубликована: Март 1, 2024
Gouty
arthritis
(GA)
is
an
immune-mediated
disorder
characterized
by
severe
inflammation
due
to
the
deposition
of
monosodium
urate
(MSU)
crystals
in
joints.
The
pathophysiological
mechanisms
GA
are
not
yet
fully
understood,
and
therefore,
identification
effective
therapeutic
targets
paramount
importance.
Neutrophil
extracellular
traps
(NETs),
intricate
structure
DNA
scaffold,
encompassing
myeloperoxidase,
histones,
elastases
-
have
gained
significant
attention
as
a
prospective
target
for
gouty
arthritis,
their
innate
antimicrobial
immunomodulatory
properties.
Hence,
exploring
potential
NETs
remains
enticing
avenue
further
investigation.
During
process
formation
triggers
release
inflammatory
cytokines,
thereby
contributing
response,
while
MSU
cytokines
sequestered
degraded
aggregation
NETs.
Here,
we
provide
concise
summary
processes
underlying
initiation
resolution
mediated
Furthermore,
this
review
presents
overview
current
pharmacological
approaches
treating
summarizes
natural
synthetic
product-based
inhibitors
that
NET
novel
options,
alongside
elucidating
intrinsic
challenges
these
research.
Lastly,
limitations
HL-60
cell
suitable
substitute
neutrophils
research
summarized
discussed.
Series
recommendations
provided,
strategically
oriented
towards
guiding
future
investigations
effectively
address
concerns.
These
findings
will
contribute
enhanced
comprehension
interplay
between
GA,
facilitating
proposition
innovative
strategies
management
GA.
Abstract
Nitrogen‐containing
drugs
represent
one
of
the
worldwide
most
extensive
sources
treatments
for
different
diseases.
Indomethacin
as
example,
is
important
non‐steroidal
anti‐inflammatories
(NSAID)
indol‐containing
drug.
Its
relevance
has
been
demonstrated
last
50
years
with
excellent
pharmacological
results.
efficacy
an
anti‐inflammatory
treatment,
inspired
us
exploration
structurally
less
elaborated
compounds
which
kept
and/or
improve
activity
compared
indomethacin.
Herein
summarized
and
discussed
our
initial
findings
on
synthesis
effect
2,3‐diarylindoles,
designed
strategically
favoring
plausible
selective
interactions
COX‐2,
route
to
new
simple
NSAID
scaffolds.
The
TPA
model
formalin
test
were
used
in
this
study
generate
inflammation
mice
conducting
assays
synthesized
2,3‐diarylindoles.
Docking
analysis
revealed
stronger
N−H
indolic
COX‐2
6‐methoxy‐2‐phenyl‐3‐(4‐chlorophenyl)‐1
H
‐indole,
active
when
This,
experimentally
match
observed
putatively
indicates
biochemical
action
mechanism.
In
the
present
research,
arsenic
nanoparticles
containing
metformin
(MTF@As
NPs)
were
synthesized
by
subjecting
a
mixture
of
As2O3
and
sodium
borohydride
solution
to
microwave
irradiation
in
presence
metformin.
The
physicochemical
properties
prepared
analyzed
using
UV-visible
spectroscopy,
Fourier
transform
infrared
spectroscopy
(FTIR),
energy-dispersive
X-ray
(EDS),
scanning
electron
microscopy
(SEM).
assessed
for
their
antioxidant
potential,
hemocompatibility,
cytotoxic
effects.
Based
on
study's
findings,
it
was
found
that
MTF@As
NPs
have
size
range
14–38
nm.
DPPH
scavenging
iron-reducing
assays
demonstrated
exhibited
significantly
higher
activity
than
As
(80–1280
µg/mL).
study
also
revealed
compatible
materials
did
not
induce
significant
hemolysis
RBCs.
According
study,
concentration
required
death
half
cells
(IC50)
treated
with
after
24
h
be
33.5
±
2.6
µg/mL
5.7
0.3
MCF-7,
NIH3T3
cells,
respectively.
Notably,
toxicity
against
MCF-7
at
concentrations
(40–1280
This
provides
insights
into
NPs,
additional
investigation
is
necessary
fully
understand
these
nanoparticles'
underlying
biological
mechanisms.
Abstract
Maleimide
core
is
a
broadly
used
chemical‐based
scaffold
for
natural
and
new
compounds
synthesis.
Several
of
them
show
anticancer
multidrug
resistance
(MDR)
reversal
activity.
A
family
twelve
3,4‐substituted
N
‐benzyl
‐methyl
maleimides
were
synthesized
in
two‐step
sequence
consisting
bromination
Suzuki
cross‐coupling
or
bromination–thiolation.
We
able
to
obtain
two
groups
maleimide
derivatives
which
tested
determining
their
cytotoxicity.
Following
our
previous
work,
the
biological
activity
these
as
MDR
agents
was
with
cancerous
cell
line
MCF‐7
that
has
been
exposed
chronically
etoposide
achieve
MDR.
resistant
(MCF‐7R),
treated
combination
synthetized
compounds.
The
results
presented
strong
effects
20
,
21
22
23
24,
25
no
cells,
IC
50
values
proliferation
inhibition
ranged
from
1.8–30.8
µM.
between
shows
increase
most
except
compound
15
where
it
shown
low
reversion
degree.
These
findings
suggest
this
work
can
be
tumorigenic
cancer
cells
before
after
acquiring
resistance.
should
evaluated
considering
an
undesirable
effect
caused
due
increase.
Asian Journal of Organic Chemistry,
Год журнала:
2023,
Номер
12(7)
Опубликована: Май 23, 2023
Abstract
Metformin
is
a
versatile,
biocompatible,
and
cheap
bis‐guanidine
used
as
first
response
line
in
the
type
II
diabetes
treatment.
Since
its
human
trials
(1956)
several
structural
modifications
were
carried
out
to
increase
activity.
However,
with
this
augmented
activity,
biological
compatibility
diminishes,
generating
serious
side
effects,
such
lactic
acidosis.
Considering
that
cytochrome
P450
oversees
metformin
metabolism
weakness
eliminate
fluorinated
metabolites;
we
envisioned
synthesis
of
benzyl
derivatives.
In
our
hypothesis
fluorine
atoms
can
give,
by
inductive
effect,
higher
acidity
hydrogen
benzylic
nitrogen,
increasing
solubility.
On
other
hand,
would
give
resistance
cP450
allowing
molecule
acting
longer.
Thus,
family
fourteen
fluorobenzyl
metformins
synthesized
characterized,
then
an
vitro
enzymatic
assay
α‐amylase
was
performed
select
five
best
performing
compounds,
vivo
experiment
streptozotocin‐induced
CD1
mice
using
selected
Blood
glucose
measured
every
day.
After
sacrifice,
lipid
profile,
serum,
liver
γ‐glutamyl
transferase
(GGT)
activity
determined
biocompatibility.
Results
showed
two
compounds
(
1
L
M
)
enhanced
biocompatibility
for
blood
glucose,
lipids
GGT
regulation.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(10), С. 1395 - 1395
Опубликована: Окт. 19, 2024
Metformin
(Met),
an
oral
drug
used
to
treat
type
II
diabetes,
is
known
control
blood
glucose
levels.
carbon
quantum
dots
(MetCQDs)
were
prepared
enhance
the
bioavailability
and
effectiveness
of
metformin.
Several
studies
have
shown
that
(CQDs)
attractive
properties
like
small
particle
size,
high
penetrability,
low
cytotoxicity,
ease
synthesis.
CQDs
are
made
from
a
source,
namely,
citric
acid,
heteroatom,
such
as
nitrogen.
The
active
molecule
can
be
source
or
reported
here.
Chemistry & Biodiversity,
Год журнала:
2023,
Номер
21(1)
Опубликована: Ноя. 28, 2023
Abstract
Multi‐Drug
Resistance
(MDR)
is
one
of
the
most
frequent
problems
observed
in
course
cancer
chemotherapy.
Cells
under
treatment,
tend
to
develop
survival
mechanisms
drug‐action
thus
generating
drug‐resistance.
One
important
mechanism
get
it
over
expression
P‐gp
glycoprotein,
which
acts
as
an
efflux‐pump
releasing
drug
outside
cell.
A
strategy
for
a
succesfull
treatment
consists
co‐administration
compound
that
against
and
another
cell
during
Ningalins
are
pyrrole‐containing
naturally
occurring
compounds
isolated
mainly
from
marine
tunicate
Didemnum
spp
also
they
some
top
reversing
agents
MDR
acting
on
P‐gp.
Considering
relevance
displayed
these
alkaloids
or
their
core
therapy,
all
total
synthesis
described
date
members
ningalins
family
reviewed
herein.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(9), С. 1234 - 1234
Опубликована: Сен. 19, 2024
N-methyl-D-aspartate
(NMDA)
receptors
are
inhibited
by
many
medicinal
drugs.
The
recent
successful
repurposing
of
NMDA
receptor
antagonists
ketamine
and
dextromethorphan
for
the
treatment
major
depressive
disorder
further
enhanced
interest
in
this
field.
In
work,
we
performed
a
screening
activity
against
native
rat
CA1
hippocampal
pyramidal
neurons
among
biguanide
compounds
using
whole-cell
patch-clamp
method.
Antimalarial
biguanides
proguanil
cycloguanil,
as
well
hypoglycemic
phenformin,
them
micromolar
concentrations,
while
another
metformin
antiviral
moroxydine
were
practically
ineffective.
IC50
values
at
−80
mV
holding
voltage
3.4
±
0.6
µM
9.0
2.2
13
1
phenformin.
inhibition
all
three
was
not
competitive.
Cycloguanil
acted
an
voltage-dependent
trapping
channel
blocker,
phenformin
allosteric
inhibitors.
Our
results
support
potential
clinical
neurodegenerative
disorders
linked
to
glutamatergic
excitotoxicity
also
providing
better
understanding
structural
determinants
antagonism
biguanides.
