Pharmaceuticals,
Journal Year:
2023,
Volume and Issue:
16(11), P. 1594 - 1594
Published: Nov. 12, 2023
A
series
of
rosmarinic
acid-β-amino-α-ketoamide
hybrids
were
synthesized
and
rationally
repurposed
towards
the
identification
new
antileishmanial
hit
compounds.
Two
hybrids,
2g
2h,
showed
promising
activity
(IC50
values
9.5
8.8
μM
against
Leishmania
donovani
promastigotes,
respectively).
Their
activities
comparable
to
erufosine.
In
addition,
cytotoxicity
evaluation
employing
human
THP-1
cells
revealed
that
two
2h
possess
no
cytotoxic
effects
up
100
µM,
while
erufosine
possessed
with
CC50
value
19.4
µM.
silico
docking
provided
insights
into
structure–activity
relationship
emphasizing
importance
aliphatic
chain
at
α-carbon
cinnamoyl
carbonyl
group
establishing
favorable
binding
interactions
LdCALP
LARG
in
both
2h.
light
these
findings,
are
suggested
as
potential
safe
compounds
for
further
development
anti-leishmanial
agents.
ACS Omega,
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 8, 2024
Leishmaniasis,
which
is
caused
by
a
parasitic
protozoan
of
the
genus
Leishmania,
still
major
threat
to
global
health,
impacting
millions
individuals
worldwide
in
endemic
areas.
Chemotherapy
has
been
principal
method
for
managing
leishmaniasis;
nevertheless,
evolution
drug
resistance
offers
significant
obstacle
therapeutic
success.
Drug-resistant
behavior
these
parasites
complex
phenomenon
including
both
innate
and
acquired
mechanisms.
Resistance
frequently
related
changes
transportation,
target
alterations,
enhanced
efflux
from
pathogen.
This
review
revealed
specific
genetic
mutations
Leishmania
that
are
associated
with
commonly
used
antileishmanial
drugs
such
as
pentavalent
antimonials,
miltefosine,
amphotericin
B,
paromomycin,
resulting
gene
expression
along
functioning
various
proteins
involved
uptake,
metabolism,
efflux.
Understanding
linked
essential
creating
approaches
tackling
avoiding
spread
drug-resistant
variants.
Based
on
treatments
focus
pathways
could
potentially
improve
treatment
efficacy
help
long-term
leishmaniasis
control.
More
study
needed
uncover
complete
range
generating
medication
develop
new
therapies
based
available
information.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: May 21, 2024
Abstract
Leishmaniasis
is
a
disease
caused
by
protozoan
of
the
genus
Leishmania
,
affecting
millions
people,
mainly
in
tropical
countries,
due
to
poor
social
conditions
and
low
economic
development.
First-line
chemotherapeutic
agents
involve
highly
toxic
pentavalent
antimonials,
while
treatment
failure
emergence
drug-resistant
strains.
arginase
(ARG)
enzyme
vital
pathogenicity
contributes
higher
infection
rate,
thus
representing
potential
drug
target.
This
study
helps
designing
ARG
inhibitors
for
leishmaniasis.
Py-CoMFA
(3D-QSAR)
models
were
constructed
using
34
from
different
chemical
classes
against
L.
(L.)
amazonensis
(
La
ARG).
The
3D-QSAR
predictions
showed
an
excellent
correlation
between
experimental
calculated
pIC
50
values.
molecular
docking
identified
favorable
hydrophobicity
contribution
phenyl
cyclohexyl
groups
as
substituents
allosteric
site.
Molecular
dynamics
simulations
selected
protein–ligand
complexes
conducted
understand
derivatives’
interaction
modes
affinity
both
active
sites.
Two
cinnamide
compounds,
7g
7k
identified,
with
similar
structures
reference
4h
site
inhibitor.
These
compounds
can
guide
development
more
effective
antileishmanial
drugs.
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(4), P. e0321219 - e0321219
Published: April 29, 2025
This
study
focused
on
evaluating
the
effectiveness
of
zinc
selenide
nanoparticles
coated
with
green
seaweed
(
Ulva
fasciata
)
(ZnSe-
Uf
against
Leishmania
major
L
.
in
light
increasing
drug
resistance
treatment
cutaneous
leishmaniasis
and
growing
necessity
for
new
therapeutic
options.
Key
characteristics
ZnSe-
,
including
shape,
size,
functional
groups,
zeta
potential,
polydispersity
index,
were
analyzed
detail.
The
investigated
effects
different
concentrations
compared
to
meglumine
antimoniate
(MA;
used
as
control),
both
promastigote
amastigote
forms
calculating
selectivity
index
(SI)
each.
Analysis
revealed
that
dominant
group
was
C-H
stretching,
attributed
polysaccharides,
lipids,
proteins.
size
ranged
from
228.2–242.8
nm
(P
=
0.37),
a
0.31–0.33
0.85),
potential
ranging
-35.6
mV
-57.9
0.07)
over
period
90
days.
lethal
concentration
50
(LC
7.61
μg/mL,
while
MA
it
17.37
μg/mL
0.03).
On
amastigote,
LC
24.3
12.3
0.04).
SI
27.55
41.26
0.02).
lower
indicated
its
better
suggesting
may
have
ability
concentrate
macrophages
MA.
However,
still
showed
anti-leishmanial
activity
non-toxic
(SI
>
10),
indicating
need
further
investigation
animal
models.
