The Journal of venomous animals and toxins including tropical diseases,
Год журнала:
2025,
Номер
31
Опубликована: Янв. 1, 2025
Abstract
Background:
Leishmaniasis
is
a
neglected
disease
that
mainly
affects
impoverished
populations
and
receives
limited
attention
from
governments
research
institutions.
Current
treatments
are
based
on
antimonial
therapies,
which
present
high
toxicity
cause
significant
side
effects,
such
as
cardiotoxicity
hepatotoxicity.
This
study
proposes
using
crotapotin,
isolated
Crotalus
durissus
terrificus
venom,
potential
inhibitor
of
the
enzyme
trypanothione
reductase
Leishmania
braziliensis
(LbTR).
Methods:
In
silico
assays
were
conducted
to
evaluate
interaction
crotapotin
with
LbTR
molecular
docking
dynamics
techniques.
Recombinant
was
expressed
in
E.
coli,
its
enzymatic
activity
confirmed.
The
inhibitory
action
then
tested
assays.
Results:
stability
these
interactions
confirmed
over
200
ns
simulations,
clustering
analysis
GROMACS
method
revealing
total
12
distinct
clusters.
five
most
representative
clusters
showed
low
RMSD
values,
indicating
structural
LbTR-crotapotin
complex.
particular,
cluster
1,
3,398
frames
an
average
0.189
nm
centroid,
suggests
dominant
stable
conformation
Additional
maintained
values
between
0.173
0.193
nm,
further
reinforcing
robustness
complex
under
physiological
conditions.
expression
successful,
yielding
4.8
mg/L
purity,
verified
by
SDS-PAGE.
assays,
partially
inhibited
activity,
IC50
223.4
μM.
Conclusion:
findings
suggest
structured
LbTR,
fluctuation,
although
inhibition
observed
vitro
moderate.
These
results
indicate
promising
basis
for
developing
specific
inhibitors,
contributing
bioprospecting
new
antiparasitic
agents.
Antimicrobial Agents and Chemotherapy,
Год журнала:
2022,
Номер
66(11)
Опубликована: Окт. 31, 2022
Drug
combinations
and
drug
repurposing
have
emerged
as
promising
strategies
to
develop
novel
treatments
for
infectious
diseases,
including
Chagas
disease.
In
this
study,
we
aimed
investigate
whether
the
repurposed
drugs
chloroquine
(CQ)
colchicine
(COL),
known
inhibit
Trypanosoma
cruzi
infection
in
host
cells,
could
boost
anti-
T.
effect
of
trypanocidal
benznidazole
(BZN),
increasing
its
therapeutic
efficacy
while
reducing
dose
needed
eradicate
parasite.
The
combination
BZN
COL
exhibited
cytotoxicity
infected
cells
low
antiparasitic
activity.
F1000Research,
Год журнала:
2023,
Номер
12, С. 93 - 93
Опубликована: Май 24, 2023
Introduction:
Leishmaniasis
is
a
disease
with
high
mortality
rates
and
approximately
1.5
million
new
cases
each
year.
Despite
the
approaches
advances
to
fight
disease,
there
are
no
effective
therapies.
Methods:
Hence,
this
study
aims
screen
for
natural
products'
structural
analogs
as
drug
candidates
against
leishmaniasis.
We
applied
Computer-aided
design
(CADD)
approaches,
such
virtual
screening,
molecular
docking,
dynamics
simulation,
mechanics-generalized
Born
surface
area
(MM-GBSA)
binding
free
estimation,
energy
perturbation
(FEP)
aiming
select
from
products
that
have
shown
anti-leishmanial
anti-arginase
activities
could
bind
selectively
Leishmania
arginase
enzyme.
Results:
The
compounds
2H-1-benzopyran,
3,4-dihydro-2-(2-methylphenyl)-(9CI),
echioidinin,
malvidin
showed
good
results
targets
three
parasite
species
negative
potential
toxicities.
echioidinin
ligands
generated
interactions
in
active
center
at
pH
2.0
conditions
by
MM-GBSA
FEP
methods.
Conclusions:
This
work
suggests
activity
of
thus
can
be
further
vitro
vivo
experimentally
validated.
Research and Reports in Tropical Medicine,
Год журнала:
2023,
Номер
Volume 14, С. 61 - 85
Опубликована: Июль 1, 2023
Leishmaniasis
is
a
neglected
tropical
disease
endemic
primarily
to
low-and
middle-income
countries,
for
which
there
has
been
inadequate
development
of
affordable,
safe,
and
efficacious
therapies.Clinical
manifestations
leishmaniasis
range
from
selfhealing
skin
lesions
lethal
visceral
infection
with
chances
relapse.Although
treatments
are
available,
secondary
effects
limit
their
use
outside
the
clinic
negatively
impact
quality
life
patients
in
areas.Other
non-medicinal
treatments,
such
as
thermotherapies,
limited
cutaneous
but
not
infection.Recent
studies
shed
light
mechanisms
through
Leishmania
can
persist
by
hiding
cellular
safe
havens,
even
after
chemotherapies.This
review
focuses
on
exploring
niches
that
parasites
may
be
leveraging
within
host.Also,
cellular,
metabolic,
molecular
implications
how
those
could
targeted
therapeutic
purposes
discussed.Other
therapies,
developed
against
cancer
or
manipulation
ferroptosis
pathway,
proposed
possible
due
action.In
particular,
target
hematopoietic
stem
cells
monocytes,
have
recently
found
necessary
components
sustain
provide
niche
discussed
this
potential
field-deployable
leishmaniasis.
The Journal of venomous animals and toxins including tropical diseases,
Год журнала:
2025,
Номер
31
Опубликована: Янв. 1, 2025
Abstract
Background:
Leishmaniasis
is
a
neglected
disease
that
mainly
affects
impoverished
populations
and
receives
limited
attention
from
governments
research
institutions.
Current
treatments
are
based
on
antimonial
therapies,
which
present
high
toxicity
cause
significant
side
effects,
such
as
cardiotoxicity
hepatotoxicity.
This
study
proposes
using
crotapotin,
isolated
Crotalus
durissus
terrificus
venom,
potential
inhibitor
of
the
enzyme
trypanothione
reductase
Leishmania
braziliensis
(LbTR).
Methods:
In
silico
assays
were
conducted
to
evaluate
interaction
crotapotin
with
LbTR
molecular
docking
dynamics
techniques.
Recombinant
was
expressed
in
E.
coli,
its
enzymatic
activity
confirmed.
The
inhibitory
action
then
tested
assays.
Results:
stability
these
interactions
confirmed
over
200
ns
simulations,
clustering
analysis
GROMACS
method
revealing
total
12
distinct
clusters.
five
most
representative
clusters
showed
low
RMSD
values,
indicating
structural
LbTR-crotapotin
complex.
particular,
cluster
1,
3,398
frames
an
average
0.189
nm
centroid,
suggests
dominant
stable
conformation
Additional
maintained
values
between
0.173
0.193
nm,
further
reinforcing
robustness
complex
under
physiological
conditions.
expression
successful,
yielding
4.8
mg/L
purity,
verified
by
SDS-PAGE.
assays,
partially
inhibited
activity,
IC50
223.4
μM.
Conclusion:
findings
suggest
structured
LbTR,
fluctuation,
although
inhibition
observed
vitro
moderate.
These
results
indicate
promising
basis
for
developing
specific
inhibitors,
contributing
bioprospecting
new
antiparasitic
agents.