New 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one derivatives as antimicrobial and anti-cancer agents: Synthesis, in-vitro and SAR studies
Journal of Molecular Structure,
Год журнала:
2023,
Номер
1294, С. 136516 - 136516
Опубликована: Авг. 30, 2023
Язык: Английский
Insight into the binding mechanisms of fluorinated 2-aminothiazole sulfonamide and human serum albumin: Spectroscopic and in silico approaches
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
277, С. 134048 - 134048
Опубликована: Авг. 6, 2024
Язык: Английский
Exploring the synthetic developments and pharmacological potential of 2-amino/hydrazino-4-arylthiazoles: a review
Journal of Sulfur Chemistry,
Год журнала:
2025,
Номер
unknown, С. 1 - 48
Опубликована: Апрель 15, 2025
Язык: Английский
Recent Progress in Thiazole, Thiosemicarbazone, and Semicarbazone Derivatives as Antiparasitic Agents Against Trypanosomatids and Plasmodium spp.
Molecules,
Год журнала:
2025,
Номер
30(8), С. 1788 - 1788
Опубликована: Апрель 16, 2025
Neglected
tropical
diseases
(NTDs),
including
Chagas
disease,
human
African
trypanosomiasis
(HAT),
leishmaniasis,
and
malaria,
remain
a
major
global
health
challenge,
disproportionately
affecting
low-income
populations.
Current
therapies
for
these
suffer
from
significant
limitations,
such
as
reduced
efficacy,
high
toxicity,
emerging
parasite
resistance,
highlighting
the
urgent
need
new
therapeutic
strategies.
In
response,
substantial
efforts
have
been
directed
toward
synthesis
of
molecules
with
improved
potency,
selectivity,
pharmacokinetic
profiles.
However,
despite
many
compounds
exhibiting
favorable
ADMET
(absorption,
distribution,
metabolism,
excretion,
toxicity)
profiles
strong
in
vitro
activity,
their
translation
into
vivo
models
remains
limited.
Key
challenges
include
lack
investment,
absence
fully
representative
experimental
models,
difficulties
extrapolating
cell-based
assay
results
to
more
complex
biological
systems.
this
review,
we
analyzed
latest
advancements
(2019–2024)
development
compound
classes,
correlating
predictive
parameters
observed
activity.
Among
parameters,
highlighted
partition
coefficient
(LogP),
which
measures
compound’s
lipophilicity
influences
its
ability
cross
membranes,
Caco-2
cell
permeability,
an
model
widely
used
predict
intestinal
drug
absorption.
Additionally,
prioritized
most
promising
structural
classes
pharmaceutical
development,
discussing
structure–activity
relationships
(SARs)
remaining
that
must
be
overcome
enable
clinical
application
treatment
NTDs.
Язык: Английский
Trypanosoma cruzi killing and immune response boosting by novel phenoxyhydrazine-thiazole against Chagas disease
Experimental Parasitology,
Год журнала:
2024,
Номер
261, С. 108749 - 108749
Опубликована: Апрель 7, 2024
Язык: Английский
Synthesis and Biological Evaluation of New Chalcogen Semicarbazone (S, Se) and Their Azole Derivatives against Chagas Disease
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(21), С. 19038 - 19056
Опубликована: Ноя. 1, 2024
Chagas
disease
is
caused
by
the
eukaryote
parasite
Trypanosoma
cruzi.
Current
treatment
exhibits
limited
efficacy
and
selenium-based
compounds
emerged
as
promising
candidates
for
new
therapies
which
surpassing
its
bioisoster,
sulfur.
We
designed
thiosemicarbazones,
thiazoles,
selenosemicarbazones
selenazoles,
using
isosteric
substitution.
synthesized
57
chalcogen
were
evaluated
against
T.
cruzi,
C2C12
cells
cruzain,
main
target
of
this
parasite.
Additionally,
human
cathepsin
L,
was
tested
selectivity.
Three
selected,
based
on
their
activity
intracellular
amastigotes
(EC50
<
1
μM,
SI
>
10)
cruzain
(IC50
100
nM,
5.55)
compared
favorably
with
approved
drug,
Benznidazole,
well-established
inhibitor
K777.
Seleno-compounds
demonstrated
enhanced
selenazoles
showed
a
decrease
in
selenium-associated
toxicity.
Compound
4-methyl-2-(2-(1-(3-nitrophenyl)ethylidene)hydrazineyl)-1,3-selenazole
(Se2h)
candidate,
binding
to
investigated.
Pharmacokinetic
assessment
conducted,
showing
favorable
profile
subsequent
vivo
assays.
Язык: Английский
Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Май 2, 2024
Abstract
According
to
the
World
Health
Organization,
Chagas
disease
(CD)
is
most
prevalent
poverty-promoting
neglected
tropical
disease.
Alarmingly,
climate
change
accelerating
geographical
spreading
of
CD
causative
parasite,
Trypanosoma
cruzi
,
which
additionally
increases
infection
rates
.
Still,
treatment
remains
challenging
due
a
lack
safe
and
efficient
drugs.
In
this
work,
we
analyze
viability
T.
Akt-
like
kinase
(
Tc
Akt)
as
drug
target
against
including
primary
structural
functional
information
about
parasitic
Akt
protein.
Nuclear
Magnetic
Resonance
derived
in
combination
with
Molecular
Dynamics
simulations
offer
detailed
insights
into
properties
pleckstrin
homology
(PH)
domain
its
binding
phosphatidylinositol
phosphate
ligands
(PIP).
Experimental
data
combined
Alpha
Fold
proposes
model
for
mechanism
action
involving
PIP-induced
disruption
intramolecular
interface
between
PH
resulting
an
open
conformation
enabling
activity.
Further
docking
experiments
reveal
that
recognized
by
human
inhibitors
PIT-1
capivasertib,
inhibition
UBMC-4
UBMC-6
achieved
via
domain.
Our
in-depth
analysis
reveals
potential
sites
development
CD,
located
at
activity
essential
regions.
Язык: Английский
DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
276, С. 116641 - 116641
Опубликована: Июль 1, 2024
Chagas
disease
is
caused
by
the
parasite
Trypanosoma
cruzi
and
affects
over
7
million
people
worldwide.
The
two
actual
treatments,
Benznidazole
(Bzn)
Nifurtimox,
cause
serious
side
effects
due
to
their
high
toxicity
leading
treatment
abandonment
patients.
In
this
work,
we
propose
DNA
G-quadruplexes
(G4)
as
potential
therapeutic
targets
for
infectious
disease.
We
have
found
174
PQS
per
100,000
nucleotides
in
genome
of
T.
confirmed
G4
formation
three
frequent
motifs.
synthesized
a
family
14
quadruplex
ligands
based
dithienylethene
(DTE)
scaffold
demonstrated
binding
these
identified
sequences.
Several
DTE
derivatives
exhibited
micromolar
activity
against
epimastigotes
four
different
strains
cruzi,
same
concentration
range
Bzn.
Compounds
L3
L4
presented
remarkable
trypomastigotes,
active
form
blood,
SOL
strain
(IC
Язык: Английский
Recent advances in medicinal chemistry of Neglected Tropical Diseases (NTDs)
European Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
259, С. 115714 - 115714
Опубликована: Авг. 7, 2023
Язык: Английский
DNA G‑Quadruplexes in the Genome of Trypanosoma Cruzi as Potential Therapeutic Targets for Chagas Disease: Dithienylethene Ligands as Effective Antiparasitic Agents
Опубликована: Янв. 1, 2024
Chagas
disease
is
caused
by
the
parasite
Trypanosoma
cruzi
and
affects
over
7
million
people
worldwide.
The
two
actual
treatments,
Benznidazole
(Bzn)
Nifurtimox,
cause
serious
side
effects
due
to
their
high
toxicity
leading
treatment
abandonment
patients.
In
this
work,
we
propose
DNA
G-quadruplexes
(G4)
as
potential
therapeutic
targets
for
infectious
disease.
We
have
found
174
putative
quadruplex
forming
sequences
per
100,000
nucleotides
in
genome
of
T.
confirmed
G4
formation
three
frequent
motifs.
synthesized
a
family
14
ligands
based
dithienylethene
(DTE)
scaffold
demonstrated
binding
these
identified
sequences.
Several
DTE
derivatives
exhibited
micromolar
activity
against
epimastigotes
four
different
strains
cruzi,
same
concentration
range
Bzn.
Compounds
L3
L4
presented
remarkable
trypomastigotes,
active
form
blood,
SOL
strain
(IC50
=
1.5-3.3
μM,
SI
=25-40.9),
being
around
40
times
more
than
Bzn
displaying
much
better
selectivity
indexes
Язык: Английский