Leishmaniasis,
an
endemic
tropical
ailment,
has
invariably
been
categorized
as
one
of
the
"neglected
diseases"
and
is
constantly
linked
with
poverty.
However,
under
current
circumstances,
it
baffling
that
leishmaniasis
no
longer
poverty-restricted.
Leishmaniasis
upheaved
its
impact
by
mushrooming
outside
zones
well
occurring
a
co-infection
many
life-threatening
infections.
Thus,
startling
even
after
afflicting
large
chunk
world's
population,
producing
critical
symptoms,
causing
several
thousands
deaths,
efforts
made
to
contain
this
disease
fall
much
shorter
than
stature
disease.
Though
noteworthy
breakthroughs
have
in
development
vaccines,
none
translated
into
commercial
success,
leaving
chemotherapy
sole
alternative.
Despite
quantum
leaps
understanding
parasite
biology,
advent
productive
silico
drug
discovery
tools,
high
throughput
screening
methods,
there
still
dearth
promising
antileishmanial
candidates
pipeline.
chapter,
we
cast
light
on
existing
therapy,
discuss
impressive
prospects
target-based
designing,
summarize
recent
advances
domain
discovery.
Inorganics,
Год журнала:
2024,
Номер
12(7), С. 190 - 190
Опубликована: Июль 12, 2024
Leishmaniasis
is
a
complex
disease
present
in
variety
of
manifestations
listed
by
the
World
Health
Organization
(WHO)
as
one
neglected
diseases
with
worse
prognosis
if
not
treated.
Medicinal
inorganic
chemistry
has
provided
drugs
based
on
metal–organic
complexes
synthesized
different
metal
centers
and
organic
ligands
to
fight
against
great
number
parasite
maladies
specifically
Leishmaniasis.
Taking
advantage
natural
properties
that
many
metals
for
biotechnological
purposes,
nanotechnology
offered,
recent
years,
new
approach
consisting
application
nanoparticles
treat
parasitic
diseases,
drug
vehicle
or
treatment
themselves.
The
aim
this
review
gather
most
widely
used
metallic
strategies
proposed
antileishmanial
agents.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 8, 2025
Parasitic
worm
infections
impose
a
significant
public
health
burden,
affecting
over
2
billion
people,
particularly
in
low-income
regions.
The
limited
efficacy
of
current
treatments
highlights
the
urgent
need
for
new
anthelmintic
agents.
This
study
investigates
potential
antiparasitic
activity
1,10-phenanthroline-5,6-dione
(phendione)
and
its
metal
complexes,
[Cu(phendione)3](ClO4)2.8H2O
[Ag(phendione)2](ClO4),
against
Schistosoma
mansoni,
causative
agent
intestinal
schistosomiasis,
Angiostrongylus
cantonensis,
responsible
eosinophilic
meningitis
humans.
Additionally,
compounds
were
tested
on
Caenorhabditis
elegans,
model
organism
drug
discovery.
All
exhibited
strong
activity,
with
Cu-phendione
showing
greatest
potency
(EC50
=
2.3
µM
S.
mansoni
6.4
A.
cantonensis).
Ag-phendione
also
demonstrated
achieving
EC₅₀
values
6.5
12.7
cantonensis.
lethal
dose
(LD50)
C.
elegans
40
times
higher,
indicating
selective
effects.
Cytotoxicity
assays
using
Vero
cells
revealed
low
toxicity
profile
high
selectivity
index.
Given
promising
biological
properties
phendione
these
findings
contribute
to
growing
body
research
seeking
address
therapies.
Tropical Medicine and Infectious Disease,
Год журнала:
2023,
Номер
8(7), С. 348 - 348
Опубликована: Июнь 30, 2023
Leishmaniasis,
caused
by
protozoa
of
the
genus
Leishmania,
encompasses
a
group
neglected
diseases
with
diverse
clinical
and
epidemiological
manifestations
that
can
be
fatal
if
not
adequately
promptly
managed/treated.
The
current
chemotherapy
options
for
this
disease
are
expensive,
require
invasive
administration
often
lead
to
severe
side
effects.
In
regard,
our
research
has
previously
reported
potent
anti-Leishmania
activity
two
coordination
compounds
(complexes)
derived
from
1,10-phenanthroline-5,6-dione
(phendione):
[Cu(phendione)3].(ClO4)2.4H2O
[Ag(phendione)2].ClO4.
present
study
aimed
evaluate
effects
these
complexes
on
leishmanolysin
(gp63),
virulence
factor
produced
all
Leishmania
species
plays
multiple
functions
is
recognized
as
potential
target
antiparasitic
drugs.
results
showed
both
Ag-phendione
(-74.82
kcal/mol)
Cu-phendione
(-68.16
were
capable
interacting
amino
acids
comprising
active
site
gp63
protein,
exhibiting
more
favorable
interaction
energies
compared
phendione
alone
(-39.75
or
1,10-phenanthroline
(-45.83
kcal/mol;
classical
inhibitor)
judged
molecular
docking
assay.
analysis
kinetic
parameters
using
fluorogenic
substrate
Z-Phe-Arg-AMC
indicated
Vmax
apparent
Km
values
0.064
µM/s
14.18
µM,
respectively,
released
gp63.
proteolytic
consistent
in
silico
assay,
where
exhibited
highest
inhibition
capacity
against
gp63,
an
IC50
value
2.16
µM
lowest
inhibitory
constant
(Ki
=
5.13
µM),
followed
(IC50
163
Ki
27.05
µM).
Notably,
pretreatment
live
L.
amazonensis
promastigotes
resulted
significant
reduction
expression
including
isoforms
located
parasite
cell
surface.
Both
markedly
decreased
vitro
association
indexes
between
THP-1
human
macrophages;
however,
effect
was
reversed
addition
soluble
molecules
medium.
Collectively,
findings
highlight
use
antivirulence
therapy
offering
new
insights
development
effective
treatments
leishmaniasis.
Pathogens,
Год журнала:
2023,
Номер
12(5), С. 745 - 745
Опубликована: Май 22, 2023
Trichomonas
vaginalis
is
responsible
for
156
million
new
cases
per
year
worldwide.
When
present
asymptomatically,
the
parasite
can
lead
to
serious
complications,
such
as
development
of
cervical
and
prostate
cancer.
As
infection
increases
acquisition
transmission
HIV,
control
trichomoniasis
represents
an
important
niche
discovery
antiparasitic
molecules.
This
urogenital
synthesizes
several
molecules
that
allow
establishment
pathogenesis
infection.
Among
them,
peptidases
occupy
key
roles
virulence
factors,
inhibition
these
enzymes
has
become
mechanism
modulating
pathogenesis.
Based
on
premises,
our
group
recently
reported
potent
anti-T.
action
metal-based
complex
[Cu(phendione)3](ClO4)2.4H2O
(Cu-phendione).
In
study,
we
evaluated
influence
Cu-phendione
modulation
proteolytic
activities
produced
by
T.
biochemical
molecular
approaches.
showed
strong
inhibitory
potential
against
peptidases,
especially
cysteine-
metallo-type
peptidases.
The
latter
revealed
a
more
prominent
effect
at
both
post-transcriptional
post-translational
levels.
Molecular
Docking
analysis
confirmed
interaction
Cu-phendione,
with
high
binding
energy
(-9.7
-10.7
kcal·mol-1,
respectively)
active
site
TvMP50
TvGP63
metallopeptidases.
addition,
significantly
reduced
trophozoite-mediated
cytolysis
in
human
vaginal
(HMVII)
monkey
kidney
(VERO)
epithelial
cell
lineages.
These
results
highlight
factors.
