Journal of Medicinal Chemistry,
Journal Year:
2020,
Volume and Issue:
63(10), P. 5341 - 5359
Published: April 29, 2020
Invasive
fungal
infections
(particularly
candidiasis)
are
emerging
as
severe
infectious
diseases
worldwide.
Because
of
serious
antifungal
drug
resistance,
therapeutic
efficacy
the
current
treatment
for
candidiasis
is
limited
and
associated
with
high
mortality.
However,
it
highly
challenging
to
develop
novel
strategies
effective
agents
combat
resistance.
Herein,
first
generation
lanosterol
14α-demethylase
(CYP51)-histone
deacetylase
(HDAC)
dual
inhibitors
was
designed,
which
exhibited
potent
activity
against
azole-resistant
clinical
isolates.
In
particular,
compounds
12h
15j
were
active
both
in
vitro
vivo
treat
candidiasis.
Antifungal
mechanism
studies
revealed
that
they
acted
by
blocking
ergosterol
biosynthesis
HDAC
catalytic
fungus,
suppressing
function
efflux
pump,
yeast-to-hypha
morphological
transition,
biofilm
formation.
Therefore,
CYP51-HDAC
represent
a
promising
strategy
Journal of Antimicrobial Chemotherapy,
Journal Year:
2019,
Volume and Issue:
75(2), P. 257 - 270
Published: Sept. 4, 2019
Abstract
Candida
albicans
is
an
opportunistic
yeast
and
the
major
human
fungal
pathogen
in
USA,
as
well
many
other
regions
of
world.
Infections
with
C.
can
range
from
superficial
mucosal
dermatological
infections
to
life-threatening
bloodstream
vital
organs.
The
azole
antifungals
remain
important
mainstay
treatment
candidiasis
therefore
investigation
understanding
evolution,
frequency
mechanisms
resistance
are
improving
strategies
against
this
organism.
Here
organism
genetic
changes
molecular
bases
underlying
currently
known
antifungal
class
reviewed,
including
up-regulated
expression
efflux
pumps,
amino
acid
composition
target
Erg11
alterations
organism’s
typical
sterol
biosynthesis
pathways.
Additionally,
we
update
what
about
activating
mutations
zinc
cluster
transcription
factor
(ZCF)
genes
regulating
these
review
import
a
potential
contributor
resistance.
Lastly,
investigations
tolerance
its
implicated
clinical
significance
reviewed.
Encyclopedia,
Journal Year:
2022,
Volume and Issue:
2(4), P. 1722 - 1737
Published: Oct. 10, 2022
Antifungal
drugs
prevent
topical
or
invasive
fungal
infections
(mycoses)
either
by
stopping
growth
of
fungi
(termed
fungistatic)
killing
the
cells
fungicidal).
Antibiotics
also
bacterial
through
bacteriostatic
bactericidal
mechanisms.
These
microorganisms
successfully
develop
resistance
against
conventional
that
are
designed
to
kill
stop
them
from
multiplying.
When
a
fungus
no
longer
responds
antifungal
drug
treatments
and
continues
grow,
this
is
known
as
resistance.
Bacteria
have
an
amazing
capacity
become
resistant
antibiotic
action
well,
effectiveness
scarce
arsenal
jeopardised
resistance,
which
poses
severe
threat
public
health.
ACS Omega,
Journal Year:
2023,
Volume and Issue:
8(20), P. 17620 - 17633
Published: May 12, 2023
Novel
thiophene-derived
Schiff
base
ligand
DE,
where
DE
is
(E)-N1,N1-diethyl-N2-(thiophen-2-ylmethylene)ethane-1,2-diamine,
and
the
corresponding
M(II)
complexes,
[M(DE)X2]
(M
=
Cu
or
Zn,
X
Cl;
M
Cd,
Br),
were
prepared
structurally
characterized.
X-ray
diffraction
studies
revealed
that
geometry
around
center
of
[Zn(DE)Cl2]
[Cd(DE)Br2],
could
be
best
described
as
a
distorted
tetrahedral.
In
vitro
antimicrobial
screening
its
[M(DE)X2],
was
performed.
The
complexes
more
potent
showed
higher
activities
against
Escherichia
coli,
Staphylococcus
aureus,
Pseudomonas
aeruginosa,
fungi
Candida
albicans,
protozoa
Leishmania
major
compared
to
ligand.
Among
studied
[Cd(DE)Br2]
exhibited
most
promising
activity
all
tested
microbes
analogs.
These
results
further
supported
by
molecular
docking
studies.
We
believe
these
may
significantly
contribute
efficient
designing
metal-derived
agents
treat
microbial
infections.
Journal of Biomolecular Structure and Dynamics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 9
Published: March 17, 2025
Azole-resistant
Candida
infections
are
on
the
rise.
Resistant
substitutions
at
Y132
in
sterol
14α-demethylase,
key
target
of
azole
drugs,
frequent.
However,
it
is
unclear
why
only
some
favoured
or
how
they
exert
differential
effects
different
azoles.
Reported
instances
were
collected
from
literature.
Extensive
molecular
dynamics
simulations
14α-demethylase
bound
to
fluconazole
VT1161
(VT1)
performed
using
GROMACS,
and
ligand-binding
free
energies
computed
quantify
various
binding/interactions.
Three
azole-resistant
substitutions,
Y
C/F/H,
reported
residue
position
132
14α-demethylase.
The
Y132H
was
most
common
substitution
C.
albicans,
while
Y132F
other
species.
Ligand-binding
−13.97
kcal/mol
−35.30
for
VT1,
respectively.
There
differences
after
compared
wild
type
protein.
frequent
Far
higher
binding
energy
comparison
with
VT1
might
partly
explain
its
susceptibility
substitutions.
results
give
insights
into
resistance,
antifungal
drug
discovery
optimization.
Antimicrobial Agents and Chemotherapy,
Journal Year:
2018,
Volume and Issue:
62(11)
Published: Aug. 16, 2018
Targeting
lanosterol
14α-demethylase
(LDM)
with
azole
drugs
provides
prophylaxis
and
treatments
for
superficial
disseminated
fungal
infections,
but
cure
rates
are
not
optimal
immunocompromised
patients
individuals
comorbidities.
The
efficacy
of
has
also
been
reduced
due
to
the
emergence
drug-resistant
pathogens.
