RSC Medicinal Chemistry,
Год журнала:
2023,
Номер
15(2), С. 492 - 505
Опубликована: Ноя. 21, 2023
Invasive
fungal
infections,
with
high
morbidity
and
mortality,
have
become
one
of
the
most
serious
threats
to
human
health.
There
are
a
few
kinds
clinical
antifungal
drugs
but
large
amounts
them
used,
so
there
is
an
urgent
need
for
new
structural
type
drug.
In
this
study,
we
carried
out
three
rounds
optimisation
modification
compound
YW-01,
which
was
obtained
from
preliminary
screening
group,
by
using
strategy
scaffold
hopping.
A
series
novel
phenylpyrimidine
CYP51
inhibitors
were
designed
synthesised.
Chemical Biology & Drug Design,
Год журнала:
2025,
Номер
105(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Invasive
fungal
infections
(IFIs)
pose
significant
challenges
in
clinical
settings,
particularly
due
to
their
high
morbidity
and
mortality
rates.
The
rising
incidence
of
these
infections,
coupled
with
increasing
antifungal
resistance,
underscores
the
urgent
need
for
novel
therapeutic
strategies.
Current
drugs
target
cell
membrane,
wall,
or
intracellular
components,
but
resistance
mechanisms
such
as
altered
drug‐target
interactions,
enhanced
efflux,
adaptive
cellular
responses
have
diminished
efficacy.
Recent
research
has
highlighted
potential
dual
inhibitors
that
simultaneously
multiple
pathways
enzymes
involved
growth
survival.
Combining
pharmacophores,
lanosterol
14α‐demethylase
(CYP51),
heat
shock
protein
90
(HSP90),
histone
deacetylase
(HDAC),
squalene
epoxidase
(SE)
inhibitors,
led
development
compounds
activity
reduced
resistance.
This
dual‐target
approach,
along
chemical
scaffolds,
not
only
represents
a
promising
strategy
combating
is
also
being
utilized
anticancer
agents.
review
explores
new
agents
employ
mono‐,
dual‐,
multi‐target
strategies
combat
IFIs.
We
discuss
emerging
targets,
mechanisms,
innovative
approaches
offer
hope
managing
challenging
infections.
Expert Opinion on Drug Delivery,
Год журнала:
2024,
Номер
21(2), С. 187 - 210
Опубликована: Янв. 20, 2024
Introduction
Amphotericin
B
(AmB),
a
promising
antifungal
and
antileishmanial
drug,
acts
on
the
membrane
of
microorganisms.
The
clinical
use
AmB
is
limited
due
to
issues
associated
with
its
delivery
including
poor
solubility
bioavailability,
instability
in
acidic
media,
intestinal
permeability,
dose
aggregation
state
dependent
toxicity,
parenteral
administration,
requirement
cold
chain
for
transport
storage,
etc.
Pharmaceutics,
Год журнала:
2024,
Номер
16(8), С. 1065 - 1065
Опубликована: Авг. 14, 2024
Polyenes
are
a
class
of
organic
compounds
well
known
for
their
potent
antifungal
properties.
They
effective
due
to
ability
target
and
disrupt
fungal
cell
membranes
by
binding
ergosterol
forming
pores.
Despite
effectiveness
as
drugs,
polyenes
have
several
limitations,
such
high
toxicity
the
host
poor
solubility
in
water.
This
has
prompted
ongoing
research
develop
safer
more
efficient
derivatives
overcome
limitations
while
enhancing
activity.
In
this
review
article,
we
present
thorough
analysis
polyene
derivatives,
structural
modifications,
influence
on
therapeutic
effects
against
various
strains.
Key
studies
discussed,
illustrating
how
modifications
led
improved
By
evaluating
latest
advancements
synthesis
highlight
that
incorporating
amide
linkers
at
carboxylic
moiety
molecules
notably
improves
properties,
evidenced
4,
5,
6G,
18.
can
help
design
development
novel
polyene-based
with
activities.
Macromolecular Bioscience,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 7, 2025
Invasive
fungal
infections
cause
over
3.7
million
deaths
worldwide
annually,
underscoring
the
critical
need
for
new
antifungal
agents.
Developing
selective
agents
is
challenging
due
to
shared
eukaryotic
nature
of
both
and
mammalian
cells.
Toward
addressing
this,
synthetic
polymers
designed
mimic
host
defense
peptides
are
promising
candidates
combating
infections.
This
study
investigates
well-defined
multiblock
terpolymers
with
specific
arrangements
cationic,
hydrophobic,
hydrophilic
groups,
as
potential
The
block
sequence
in
these
copolymers
significantly
impacts
their
minimum
inhibition
concentration
(MIC)
against
Candida
albicans
biocompatibility.
Furthermore,
compared
statistical
counterparts,
exhibit
lower
MIC
values
certain
instances.
Notably,
triblock
containing
a
central
hydrophobic
present
an
enhanced
efficacy
These
findings
highlight
sequence-controlled
versatile
platform
developing
customized
targeted
therapies.
Archiv der Pharmazie,
Год журнала:
2025,
Номер
358(5)
Опубликована: Май 1, 2025
ABSTRACT
Aiming
at
developing
a
new
class
of
quaternary
pyridinium
salts,
the
lead
compound
1
,
characterized
by
pyridine‐3‐yl
chalcone
framework,
was
rationally
modified
inserting
alkyl
functions
varying
from
6
to
18
carbon
units.
Among
set,
some
valuable
compounds
were
identified.
Derivatives
4
–
primarily
active
against
Staphylococcus
aureus
and
Candida
albicans
respectively
(MIC
=
1.56
3.125
μM).
In
comparison,
analogs
5
showed
significant
activities
Escherichia
coli
6.25
Interestingly,
antimicrobial
property
as
well
their
antibiofilm
activity,
occurred
lower
concentrations
than
cyto‐
erythrocyte
toxicities,
thus
ensuring
favorable
safety
profile.
Structure–activity
relationship
analysis
highlighted
critical
role
tail
length
in
optimal
results
observed
for
moieties
ranging
10
14
Molecular
dynamics
studies
performed
on
2
modeling
them
Gram‐positive
Gram‐negative
membranes
that
derivatives,
upon
diffusing
across
periodic
boundary
conditions,
able
intercalate
into
microbial
membranes.
The
difference
diffusion
rates
provides
useful
information
support
diverse
potencies
newly
designed
salt.
ACS Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 13, 2025
The
escalating
incidence
of
antimicrobial
resistance
to
antifungal
agents,
alongside
the
emergence
drug-resistant
fungal
strains,
constitutes
a
significant
threat
potential
global
pandemic.
In
response,
researchers
are
intensifying
efforts
identify
novel
compounds
through
diverse
methodologies.
Emerging
strategies
focus
on
innovative
therapeutic
targets
that
may
reduce
risk
development
while
offering
broad-spectrum
efficacy
against
infections.
Additionally,
these
approaches
present
cost-effectiveness
and
accelerated
timelines.
This
review
systematically
categorizes
range
compounds,
including
peptides,
cationic
amphiphiles,
small
molecules,
polymers,
repurposed
drugs,
based
their
in
inhibiting
growth
associated
virulence
factors.
These
exhibit
notable
activity
across
silico,
vitro,
vivo
systems
various
pathogenic
with
several
showing
substantial
promise
for
clinical
application.
Furthermore,
highlights
limitations
standard
antifungals
elucidates
mechanisms
by
which
strains
develop
resistance.
work
aims
engage
distinctive
field
biology
foster
exploration
new
strategies.
Abstract
Non‐polymeric
small
amphiphiles
have
attained
a
significant
role
in
various
applications
due
to
their
defined
and
consistent
molecular
assembly
hydrophobic/lipophilic
balance.
Synthesized
Amphiphiles
2‐(5‐(bis(dodecylthio)methyl)‐2‐hydroxyphenyl)quinazolin‐4(3H)‐one
(Q‐C12)
has
been
recognized
as
new
amphiphiles.
The
structurally
Q‐C12
fluorescent
quinazolinone
moiety
attached
with
two
sulfur
centers
long
alkyl
chains.
structural
uniqueness
of
for
the
presence
sulfur‐based
chain
backbone
makes
it
selective
towards
detection
mercury
(Hg
2
⁺)
ions,
followed
by
scavenging
from
aqueous
system.
It
also
shows
its
ability
detect
bind
diethyl
chlorophosphate
(DCP),
toxic
stimulant
nerve
agents,
using
fluorescence
efficacy.
Each
observation
well
studied
NMR,
fluorescence,
DLS
analysis.
Further,
behaves
very
effectively
an
anti‐yeast
agent.
yeast
cell
imaging
study
captured
against
Pichia
sp.
strain
KG2
Fluorescent
Q‐C12.
development
low‐cost
functional
amphiphile,
claims
great
promise
environmental
monitoring,
advanced
material,
biomedical
innovations,
offers
multifunctional
approach
addressing
key
challenges
pollution
control
healthcare.
RSC Pharmaceutics,
Год журнала:
2024,
Номер
1(2), С. 372 - 378
Опубликована: Янв. 1, 2024
The
antifungal
activity
of
a
small
chitin-binding
domain
from
chitinase
was
enhanced
by
the
artificial
lipidation
with
specific
alkyl
chain
length
and
structure
in
presence
amphotericin
B.
