ACS Omega,
Journal Year:
2025,
Volume and Issue:
10(17), P. 18116 - 18124
Published: April 25, 2025
Chagas
disease
remains
a
significant
global
health
problem.
Current
etiological
treatment
is
limited
due
to
its
low
efficacy
in
the
advanced
stage
of
and
adverse
effects.
Trypanosoma
cruzi
dihydroorotate
dehydrogenase
(TcDHODH)
promising
target
for
developing
new
drugs.
This
study
explored
structural
dynamic
factors
influencing
inhibition.
The
results
from
100
ns
molecular
dynamics
simulations
11
ligand-TcDHODH
complexes
revealed
that
ligand
size
conformation
play
crucial
roles
enzyme
inhibition,
with
flexibility
active
site
being
essential
function.
Small
ligands
tend
maintain
closed
conformation,
while
larger
induce
open
conformations.
further
demonstrate
ligand-induced
conformational
changes
role
key
hydrogen
bonds
stabilizing
ligand-enzyme
complex.
Electrostatic
hydrophobic
interactions
between
enzyme's
S1,
S2,
S3
subsites
contribute
Understanding
these
facilitates
development
potent
selective
TcDHODH
inhibitors
disease.
ACS Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
10(3), P. 938 - 950
Published: Feb. 8, 2024
The
search
for
new
anti-infectives
based
on
metal
complexes
is
gaining
momentum.
Among
the
different
options
taken
by
researchers,
one
involving
use
of
organometallic
probably
most
successful
with
a
compound,
namely,
ferroquine,
already
in
clinical
trials
against
malaria.
In
this
study,
we
describe
preparation
and
in-depth
characterization
10
(organometallic)
derivatives
approved
antifungal
drug
fluconazole.
Our
rationale
that
sterol
14α-demethylase
an
enzyme
part
ergosterol
biosynthesis
route
Trypanosoma
similar
to
pathogenic
fungi.
To
demonstrate
our
postulate,
docking
experiments
assess
binding
compounds
were
also
performed.
then
tested
range
fungal
strains
parasitic
organisms,
including
protozoan
parasite
cruzi
(T.
cruzi)
responsible
Chagas
disease,
endemic
disease
Latin
America
ranks
among
some
prevalent
diseases
worldwide.
Of
high
interest,
two
potent
study
T.
contain
ferrocene
or
cobaltocenium
found
be
harmless
invertebrate
animal
model,
Caenorhabditis
elegans
(C.
elegans),
without
affecting
motility,
viability,
development.
Frontiers in Chemistry,
Journal Year:
2022,
Volume and Issue:
9
Published: Jan. 7, 2022
Human
African
Trypanosomiasis
(HAT),
Chagas
disease
or
American
(CD),
and
leishmaniases
are
protozoan
infections
produced
by
trypanosomatid
parasites
belonging
to
the
kinetoplastid
order
they
constitute
an
urgent
global
health
problem.
In
fact,
there
is
need
of
more
efficient
less
toxic
chemotherapy
for
these
diseases.
Medicinal
inorganic
chemistry
currently
offers
attractive
option
rational
design
new
drugs
and,
in
particular,
antiparasitic
ones.
this
sense,
one
main
strategies
metal-based
compounds
has
been
coordination
organic
ligand
with
known
potential
biological
activity,
a
metal
centre
organometallic
Future Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
16(3), P. 221 - 238
Published: Jan. 25, 2024
Aim:
To
synthesize
novel
more
potent
trypanocidal
and
leishmanicidal
agents.
Methods:
Hantzsch's
synthetic
strategy
was
used
to
1,3-thiazole-4-carboxylates
their
N-benzylated
derivatives.
Results:
28
new
thiazole-carboxylates
derivatives
were
established
test
activities.
From
both
series,
compounds
3b,
4f,
4g,
4j
4n
exhibited
a
better
or
comparable
profile
benznidazole.
Among
all
tested
compounds,
found
be
the
most
than
Conclusion:
Further
variation
of
substituents
around
hydrazinyl
moiety
may
assist
in
establishing
International Journal of Molecular Sciences,
Journal Year:
2019,
Volume and Issue:
20(23), P. 5916 - 5916
Published: Nov. 25, 2019
Trypanosoma
species
are
responsible
for
chronic
and
systemic
infections
in
millions
of
people
around
the
world,
compromising
life
quality,
family
government
budgets.
This
group
diseases
is
classified
as
neglected
causes
thousands
deaths
each
year.
In
present
study,
trypanocidal
effect
a
set
12
ester
derivatives
p-coumaric
acid
was
tested.
Of
test
derivatives,
pentyl
p-coumarate
(7)
(5.16
±
1.28
μM;
61.63
28.59
μM)
presented
best
respective
activities
against
both
epimastigote
trypomastigote
forms.
Flow
cytometry
analysis
revealed
an
increase
percentage
7-AAD
labeled
cells,
reactive
oxygen
species,
loss
mitochondrial
membrane
potential;
indicating
cell
death
by
necrosis.
mechanism
confirmed
scanning
electron
microscopy,
noting
cellular
integrity.
Molecular
docking
data
indicated
that
chemical
compounds
tested,
compound
7
potentially
acts
through
two
mechanisms
action,
whether
links
with
aldo-keto
reductases
(AKR)
or
comprising
cruzain
(CZ)
which
one
key
cruzi
development
enzymes.
The
results
indicate
enzymes,
van
der
Waals
interactions
between
ligand
receptors
favor
binding
hydrophobic
phenolic
aliphatic
parts
ligand.
study
demonstrates
promising
molecules
developing
new
prototypes
antiprotozoal
activity.
European Journal of Organic Chemistry,
Journal Year:
2019,
Volume and Issue:
2019(13), P. 2344 - 2353
Published: Jan. 8, 2019
Ruthenium(II)‐catalysis
enabled
C–H
alkenylations
of
unactivated
naphthoquinones
for
the
preparation
A‐ring‐modified
naphthoquinoidal
compounds
with
activity
against
Trypanosoma
cruzi
,
parasite
causing
Chagas
disease.
The
present
study
encompasses
alkenylation
by
weak
O
‐coordination
means
ruthenium(II)
carboxylates.
This
method
provided
an
efficient
and
versatile
tool
towards
a
diversity‐oriented
strategy
relevant
biological
profile.
Expert Opinion on Investigational Drugs,
Journal Year:
2020,
Volume and Issue:
29(9), P. 947 - 959
Published: July 7, 2020
ABSTRACT
Introduction
Chagas
disease
treatment
relies
on
the
lengthy
administration
of
benznidazole
and/or
nifurtimox,
which
have
frequent
toxicity
associated.
The
disease,
caused
by
parasite
Trypanosoma
cruzi,
is
mostly
diagnosed
at
its
chronic
phase
when
life-threatening
symptomatology
manifest
in
approximately
30%
those
infected.
Considering
that
both
available
drugs
variable
efficacy
then,
and
there
are
over
6
million
people
infected,
a
pressing
need
to
find
safer,
more
efficacious
drugs.
Areas
covered
We
provide
an
updated
view
path
achieve
aforementioned
goal.
From
state-of-the-art
vitro
vivo
assays
based
genetically
engineered
parasites
allowed
high
throughput
screenings
large
chemical
collections,
unfulfilled
requirement
having
treatment-response
biomarkers
for
clinical
evaluation
In
between,
we
describe
most
promising
pre-clinical
hits
landscape
trials
with
new
or
regimens
existing
ones.
Moreover,
use
monkey
models
reduce
attrition
rate
discussed.
Expert
opinion
addition
necessary
research
much
awaited
efficacy,
key
step
will
be
generalize
access
diagnosis
maximize
efforts
impede
transmission.
ACS Infectious Diseases,
Journal Year:
2020,
Volume and Issue:
6(11), P. 2830 - 2843
Published: Oct. 9, 2020
Chagas
disease
is
a
neglected
tropical
and
global
public
health
issue.
In
terms
of
treatment,
no
progress
has
been
made
since
the
1960s,
when
benznidazole
nifurtimox,
two
obsolete
drugs
still
prescribed,
were
used
to
treat
this
disease.
Hence,
currently,
there
are
effective
treatments
available
tackle
Over
past
20
years,
an
increasing
interest
in
However,
parasite
genetic
diversity,
drug
resistance,
tropism,
complex
life
cycle,
along
with
limited
understanding
inadequate
methodologies
strategies,
have
resulted
absence
new
insights
development
disappointing
outcomes
clinical
trials
so
far.
summary,
urgently
needed.
This
Review
considers
relevant
aspects
related
lack
for
disease,
resumes
advances
tools
discovery,
discusses
main
features
be
taken
into
account
develop
drugs.
