Pharmaceuticals,
Год журнала:
2024,
Номер
17(12), С. 1680 - 1680
Опубликована: Дек. 12, 2024
Background/Objectives:
Infectious
diseases
represent
a
serious
threat
due
to
rising
antimicrobial
resistance,
particularly
among
multidrug-resistant
bacteria
and
influenza
viruses.
Metal-based
complexes,
such
as
N-heterocyclic
carbene–gold
(NHC–gold)
show
promising
therapeutic
potential
their
ability
inhibit
various
pathogens.
Methods:
Eight
NHC–gold
complexes
were
synthesized
tested
for
antibacterial
activity
against
Escherichia
coli,
Enterococcus
faecalis,
Staphylococcus
aureus,
anti-influenza
in
lung
bronchial
epithelial
cells
infected
with
virus
A/H1N1.
Antibacterial
was
assessed
through
the
determination
of
minimum
inhibitory
concentration
(MIC)
bactericidal
(MBC),
while
viral
load
quantified
using
qRT-PCR.
Results:
Complexes
3,
4,
6
showed
significant
at
concentrations
10–20
µg/mL.
Additionally,
these
significantly
reduced
load,
3
4
markedly
inhibiting
replication.
Conclusions:
These
findings
support
use
combined
antiviral
therapies,
representing
an
attractive
option
fighting
resistant
infections.
Medicinal Research Reviews,
Год журнала:
2024,
Номер
44(5), С. 2194 - 2235
Опубликована: Апрель 9, 2024
Abstract
Metal
complexes
based
on
N
‐heterocyclic
carbene
(NHC)
ligands
have
emerged
as
promising
broad‐spectrum
antitumor
agents
in
bioorganometallic
medicinal
chemistry.
In
recent
decades,
studies
cytotoxic
metal–NHC
yielded
numerous
compounds
exhibiting
superior
cytotoxicity
compared
to
cisplatin.
Although
the
molecular
mechanisms
of
these
anticancer
are
not
fully
understood,
some
potential
targets
and
modes
action
been
identified.
However,
a
comprehensive
review
their
biological
is
currently
absent.
general,
apoptosis
caused
by
metal–NHCs
common
tumor
cells.
They
can
cause
series
changes
after
entering
cells,
such
mitochondrial
membrane
(MMP)
variation,
reactive
oxygen
species
(ROS)
generation,
cytochrome
c
(cyt
c)
release,
endoplasmic
reticulum
(ER)
stress,
lysosome
damage,
caspase
activation,
ultimately
leading
apoptosis.
Therefore,
detailed
understanding
influence
cancer
cell
crucial.
this
review,
we
provide
summary
advances
that
trigger
apoptotic
death
via
different
apoptosis‐related
or
signaling
pathways,
including
B‐cell
lymphoma
2
(Bcl‐2
family),
p53,
cyt
c,
ER
thioredoxin
reductase
(TrxR)
inhibition,
so
forth.
We
also
discuss
challenges,
limitations,
future
directions
elucidate
emerging
application
ACS Infectious Diseases,
Год журнала:
2024,
Номер
10(5), С. 1753 - 1766
Опубликована: Апрель 12, 2024
The
antibacterial
activity
of
silver
species
is
well-established;
however,
their
mechanism
action
has
not
been
adequately
explored.
Furthermore,
issues
low-molecular
compounds
with
cytotoxicity,
stability,
and
solubility
hamper
progress
to
drug
leads.
We
have
investigated
N-heterocyclic
carbene
(NHC)
halido
complexes
[(NHC)AgX,
X
=
Cl,
Br,
I]
as
a
promising
new
type
organometallics.
Spectroscopic
studies
conductometry
established
higher
stability
for
the
iodide
ligands,
nephelometry
indicated
that
could
be
administered
in
solutions
physiological
chloride
levels.
showed
broad
spectrum
strong
against
pathogenic
Gram-negative
bacteria.
However,
there
was
no
significant
Gram-positive
strains.
Further
clarified
tryptone
yeast
extract,
components
culture
media,
were
responsible
this
lack
activity.
reduction
biofilm
formation
inhibition
both
glutathione
thioredoxin
reductases
IC50
values
nanomolar
range
confirmed
selected
compounds.
In
addition
improved
physicochemical
properties,
ligands
did
display
cytotoxic
effects,
unlike
other
complexes.
summary,
NHC
secondary
represent
useful
scaffold
nontoxic
organometallics
properties
distinct
based
on
reductases.
In
recent
years,
the
number
of
people
suffering
from
cancer
has
risen
rapidly
and
World
Health
Organization
U.S.
European
governments
have
identified
this
pathology
as
a
priority
issue.
It
is
known
that
most
bioactive
anticancer
molecules
do
not
target
single
protein
but
exert
pleiotropic
effects,
simultaneously
affecting
multiple
pathways.
our
study,
we
designed
synthesized
new
series
silver
N-heterocyclic
carbene
(NHC)
complexes
[(NHC)
Antibiotics,
Год журнала:
2023,
Номер
12(2), С. 365 - 365
Опубликована: Фев. 9, 2023
Ruthenium
N-heterocyclic
carbene
(NHC)
complexes
have
unique
physico-chemical
properties
as
catalysts
and
a
huge
potential
in
medicinal
chemistry
pharmacology,
exhibiting
variety
of
notable
biological
activities.
In
this
review,
the
most
recent
studies
on
ruthenium
NHC
are
summarized,
focusing
specifically
antimicrobial
antiproliferative
generally
active
against
Gram-positive
bacteria,
such
Bacillus
subtilis,
Staphylococcus
aureus,
Micrococcus
luteus,
Listeria
monocytogenes
seldom
Gram-negative
including
Salmonella
typhimurium,
Pseudomonas
aeruginosa
Escherichia
coli
fungal
strains
Candida
albicans.
The
activity
was
tested
cancer
cell
lines
human
colon,
breast,
cervix,
epidermis,
liver
rat
glioblastoma
lines.
demonstrated
cytotoxicity
higher
than
standard
anticancer
drugs.
Further
needed
to
explore
mechanism
action
these
interesting
compounds.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(2), С. 1507 - 1507
Опубликована: Янв. 12, 2023
Electrospun
systems
are
becoming
promising
devices
usable
for
topical
treatments.
They
eligible
to
deliver
different
therapies,
from
anti-inflammatory
antitumoral.
In
the
current
research,
polycaprolactone
electrospun
membranes
loaded
with
synthetic
and
commercial
antitumoral
active
substances
were
produced,
underlining
how
matrix-filler
affinity
is
a
crucial
parameter
designing
drug
delivery
devices.
Nanofibrous
percentages
of
Dacarbazine
(the
choice
melanoma)
derivative
produced
compared
AuM1,
highly
Au-complex
low
matrix.
AFM
morphologies
showed
that
surface
profile
nanofibers
affine
similar
one
unloaded
systems,
thanks
nature
interaction.
FTIR
analyses
proved
efficacy
interaction
between
amidic
group
polycaprolactone.
AuM1-loaded
membranes,
because
weak
interaction,
complex
mainly
aggregated
in
nanometric
domains
on
nanofiber
surface,
which
manifests
roughness.
Consequently,
release
profiles
follow
Fickian
behavior
Dacarbazine-based
whereas
two-step
prominent
burst
effect
was
observed
AuM1
systems.
The
performed
tests
evidence
high-cytotoxic
activity
against
melanoma
cell
lines,
proving
more
than
dacarbazine.
Applied Sciences,
Год журнала:
2024,
Номер
14(19), С. 8865 - 8865
Опубликована: Окт. 2, 2024
This
study
investigates
the
antibacterial
N-heterocyclic
carbene
(NHC)–silver
complexes
using
SwissADME
platform,
a
web-based
tool
developed
by
Swiss
Institute
of
Bioinformatics
(SIB).
NHCs,
particularly
their
silver
complexes,
have
gained
significant
interest
in
medicinal
chemistry
for
potential
as
and
anticancer
agents.
The
effectiveness
these
is
closely
linked
to
structure,
including
factors
like
lipophilicity,
which
enhance
ability
penetrate
bacterial
cells
sustain
release
active
ions.
provides
computational
estimates
pharmacokinetic
properties,
absorption,
distribution,
metabolism,
excretion
(ADME)
characteristics,
well
drug-likeness
toxicity
assessments.
By
evaluating
parameters
molecular
weight,
topological
polar
surface
area,
lipophilicity
(LogP),
water
solubility,
offers
insights
into
drug-like
compounds.
inspired
comprehensive
review
NHC–silver
published
from
2006
2023,
identified
superior
structures
with
notable
biological
activity.
primary
aim
determine
whether
exhibit
distinct
compared
others,
providing
deeper
understanding
that
influence
efficacy
aiding
identification
promising
drug
candidates.
Finally,
experimental
stabilities
exemplary
were
confronted
absolute
LUMO
values
derived
DFT
calculations.
This
article
reports
the
synthesis,
characterization,
and
antitumor
properties
of
newly
synthesized
benzimidazole-based
Ag(I)-(BNHCs)
complexes
from
their
proligands.
All
compounds
underwent
comprehensive
characterization
using
techniques
such
as
1H,
COSY,
13C
NMR,
IR
spectroscopy,
electrospray
ionization
(ESI)-mass,
elemental,
single-crystal
X-ray
diffraction
(XRD)
analysis.
Density
functional
theory
(DFT)
studies
were
carried
out
to
observe
electronic
effects
bound
ligands
modulate
selectivity
reactivity
silver
complexes.
Time-dependent
DFT
(TD-DFT)
assessed
optical
further
highlighted
by
orbital
contributions
with
oscillator
strengths.
tested
against
breast
cancer
MCF-7
T47D
cell
lines.
The
synergistic
benzimidazole-incorporated
aryl
constituent
structuring
also
observed.
Nearly
all
have
been
found
be
promising
anticancer
agents
added
benefit
low
cytotoxic
toward
normal
cells.
Intriguingly,
[AgL
4
(Cl)]
exhibited
best
activity
among
our
screened
IC50
values
for
both
9
±
1.04
11
1.41,
respectively.
apoptosis
mode
death
was
confirmed
phosphatidylserine
exposure
annexin
V/PI
staining
imaging
method.
CT-DNA
interactions
most
active
complex
([AgL
(Cl)])
its
proligand
(HL
(Cl))
support
compound-DNA
interaction.
Strong
DNA
binding
affinities
(K
b)
through
electrostatic
intercalation
modes
induced
structural
changes
in
DNA.
Moreover,
molecular
docking
comprehend
possible
various
receptors
EGFR
(epidermal
growth
factor
receptor),
VEGFR2
(vascular
endothelial
receptors),
FGFR
(fibroblast
SRC
(proto-oncogene
tyrosine
kinase
protein)
family
serves
crucial
cancer.