European Journal of Pharmaceutical Sciences,
Год журнала:
2025,
Номер
207, С. 107041 - 107041
Опубликована: Фев. 12, 2025
Heat
shock
protein
90
(Hsp90)
is
a
pivotal
virulence
factor
in
pathogenic
fungi,
playing
significant
role
conferring
drug
resistance.
However,
due
to
the
high
amino
acid
sequence
similarity
between
fungal
and
mammalian
Hsp90,
targeting
intracellular
Hsp90
therapeutically
associated
with
marked
toxic
side
effects,
thereby
limiting
clinical
application.
Studies
have
demonstrated
that
can
be
secreted
as
extracellular
(eHsp90),
which
plays
crucial
infections.
Strategies
eHsp90
exhibited
promising
therapeutic
outcomes.
Unlike
targeting,
such
antifungal
approaches
operate
without
cell
penetration,
circumventing
effects
Hsp90's
conservation.
This
review
summarizes
potential
secretion
pathways
of
eHsp90,
its
roles
pathogenesis,
well
development
vaccines
antibodies
eHsp90.
The
underlines
significance
infections
suggests
represents
target
for
infection
treatment.
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.
Molecules,
Год журнала:
2024,
Номер
29(5), С. 999 - 999
Опубликована: Фев. 25, 2024
The
use
of
natural
compounds
to
prevent
and
treat
infective
diseases
is
increasing
its
importance,
especially
in
the
case
multidrug-resistant
(MDR)
microorganisms-mediated
infections.
drug
resistance
phenomenon
today
a
global
problem,
so
it
important
have
available
substances
able
counteract
MDR
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2024,
Номер
14
Опубликована: Фев. 9, 2024
In
the
last
twenty
years,
there
has
been
a
significant
increase
in
invasive
fungal
infections,
which
corresponded
with
expanding
population
of
individuals
compromised
immune
systems.
As
result,
mortality
rate
linked
to
these
infections
remains
unacceptably
high.
The
currently
available
antifungal
drugs,
such
as
azoles,
polyenes,
and
echinocandins,
face
limitations
terms
their
diversity,
escalating
resistance
fungi
occurrence
adverse
effects.
Consequently,
is
an
urgent
need
develop
new
medications.
Vaccines
antibodies
present
promising
avenue
for
addressing
due
targeted
properties
ability
modulate
response.
This
review
investigates
structure
function
cell
wall
proteins,
secreted
functional
proteins
within
C.
albicans
.
Furthermore,
it
seeks
analyze
current
advancements
challenges
macromolecular
drugs
identify
targets
effective
management
candidiasis.
ACS Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
The
emergence
of
azole
resistance
and
tolerance
in
pathogenic
fungi
has
emerged
as
a
significant
public
health
concern,
emphasizing
the
urgency
for
innovative
strategies
to
bolster
efficacy
azole-based
treatments.
Drug
repurposing
stands
promising
practical
avenue
advancing
antifungal
therapy,
with
potential
swift
clinical
translation.
This
review
offers
comprehensive
overview
synergistic
agents
uncovered
through
drug
strategies,
alongside
an
in-depth
exploration
mechanisms
by
which
these
augment
potency.
Drawing
from
mechanisms,
we
delineate
aimed
at
enhancing
effectiveness,
such
inhibiting
efflux
pumps
elevate
concentrations
within
fungal
cells,
intensifying
ergosterol
synthesis
inhibition,
mitigating
cell
azoles,
disrupting
biological
processes
extending
beyond
synthesis.
is
beneficial
development
potentiators,
it
meticulously
examines
instances
provides
nuanced
discussions
on
underlying
progression
potentiators
strategies.
Biomolecules,
Год журнала:
2023,
Номер
13(11), С. 1572 - 1572
Опубликована: Окт. 24, 2023
Invasive
fungal
infections
present
a
significant
risk
to
human
health.
The
current
arsenal
of
antifungal
drugs
is
hindered
by
drug
resistance,
limited
range,
inadequate
safety
profiles,
and
low
oral
bioavailability.
Consequently,
there
an
urgent
imperative
develop
novel
medications
for
clinical
application.
This
comprehensive
review
provides
summary
the
properties
mechanisms
exhibited
natural
polyketides,
encompassing
macrolide
polyethers,
polyether
xanthone
linear
hybrid
polyketide
non-ribosomal
peptides,
pyridine
derivatives.
Investigating
compounds
their
derivatives
has
demonstrated
remarkable
efficacy
promising
application
as
agents.
Antioxidants,
Год журнала:
2024,
Номер
13(2), С. 223 - 223
Опубликована: Фев. 9, 2024
Candida
albicans,
a
prominent
opportunistic
pathogenic
fungus
in
the
human
population,
possesses
capacity
to
induce
life-threatening
invasive
candidiasis
individuals
with
compromised
immune
systems
despite
existence
of
antifungal
medications.
When
faced
macrophages
or
neutrophils,
C.
albicans
demonstrates
its
capability
endure
oxidative
stress
through
utilization
antioxidant
enzymes.
Therefore,
enhancement
innate
cells
against
presents
promising
therapeutic
approach
for
treatment
candidiasis.
In
this
study,
we
conducted
comprehensive
analysis
library
drugs
approved
by
Food
and
Drug
Administration
(FDA).
We
discovered
that
halofantrine
hydrochloride
(HAL)
can
augment
properties
damage
agents
(plumbagin,
menadione,
H2O2)
suppressing
response
reactive
oxygen
species
(ROS).
Furthermore,
our
investigation
revealed
inhibitory
mechanism
HAL
on
is
dependent
Cap1.
addition,
activity
has
been
observed
Galleria
mellonella
infection
model.
These
findings
provide
evidence
targeting
augmenting
fungicidal
hold
promise
as
effective
strategies.
Marine Drugs,
Год журнала:
2024,
Номер
22(4), С. 180 - 180
Опубликована: Апрель 17, 2024
The
incidence
of
invasive
fungal
diseases
(IFDs)
is
on
the
rise
globally,
particularly
among
immunocompromised
patients,
leading
to
significant
morbidity
and
mortality.
Current
clinical
antifungal
agents,
such
as
polyenes,
azoles,
echinocandins,
face
increasing
resistance
from
pathogenic
fungi.
Therefore,
there
a
pressing
need
for
development
novel
drugs.
Marine-derived
secondary
metabolites
represent
valuable
resources
that
are
characterized
by
varied
chemical
structures
pharmacological
activities.
While
numerous
compounds
exhibiting
promising
activity
have
been
identified,
comprehensive
review
elucidating
their
specific
underlying
mechanisms
remains
lacking.
In
this
review,
we
compiled
summary
derived
marine
organisms,
highlighting
diverse
action
targeting
various
cellular
components,
including
cell
wall,
membrane,
mitochondria,
chromosomes,
drug
efflux
pumps,
several
biological
processes,
vesicular
trafficking
growth
hyphae
biofilms.
This
helpful
subsequent
drugs
due
its
organisms.
