Navigating the Chemical Space and Chemical Multiverse of a Unified Latin American Natural Product Database: LANaPDB
Pharmaceuticals,
Год журнала:
2023,
Номер
16(10), С. 1388 - 1388
Опубликована: Сен. 30, 2023
The
number
of
databases
natural
products
(NPs)
has
increased
substantially.
Latin
America
is
extraordinarily
rich
in
biodiversity,
enabling
the
identification
novel
NPs,
which
encouraged
both
development
and
implementation
those
that
are
being
created
or
under
development.
In
a
collective
effort
from
several
American
countries,
herein
we
introduce
first
version
Natural
Products
Database
(LANaPDB),
public
compound
collection
gathers
chemical
information
NPs
contained
diverse
this
geographical
region.
current
LANaPDB
unifies
six
countries
contains
12,959
structures.
structural
classification
showed
most
abundant
compounds
terpenoids
(63.2%),
phenylpropanoids
(18%)
alkaloids
(11.8%).
From
analysis
distribution
properties
pharmaceutical
interest,
it
was
observed
many
satisfy
some
drug-like
rules
thumb
for
physicochemical
properties.
concept
multiverse
employed
to
generate
multiple
spaces
two
different
fingerprints
dimensionality
reduction
techniques.
Comparing
with
FDA-approved
drugs
major
open-access
repository
COCONUT,
concluded
space
covered
by
completely
overlaps
COCONUT
and,
regions,
drugs.
will
be
updated,
adding
more
each
database,
plus
addition
other
countries.
Язык: Английский
Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp
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.
Язык: Английский
Targeting with Structural Analogs of Natural Products the Purine Salvage Pathway in Leishmania (Leishmania) infantum by Computer-Aided Drug-Design Approaches
Tropical Medicine and Infectious Disease,
Год журнала:
2024,
Номер
9(2), С. 41 - 41
Опубликована: Фев. 3, 2024
Visceral
Leishmaniasis
(VL)
has
a
high
death
rate,
with
500,000
new
cases
and
50,000
deaths
occurring
annually.
Despite
the
development
of
novel
strategies
technologies,
there
is
no
adequate
treatment
for
disease.
Therefore,
purpose
this
study
to
find
structural
analogs
natural
products
as
potential
drugs
treat
VL.
We
selected
from
that
have
shown
antileishmanial
activities,
may
impede
purine
salvage
pathway
using
computer-aided
drug-design
(CADD)
approaches.
For
these,
we
started
vastly
studied
target
in
pathway,
adenine
phosphoribosyl
transferase
(APRT)
protein,
which
alone
non-essential
survival
parasite.
Keeping
mind,
search
substance
can
bind
multiple
targets
throughout
pathway.
Computational
techniques
were
used
Leishmania
infantum,
molecular
dynamic
simulations
gather
information
on
interactions
between
ligands
proteins.
Because
its
low
homology
human
proteins
essential
role
network
interaction,
findings
further
highlight
significance
adenylosuccinate
lyase
protein
(ADL)
therapeutic
target.
An
analog
alkaloid
Skimmianine,
N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide,
demonstrated
good
binding
affinity
APRT
ADL
targets,
expected
toxicity,
oral
route
administration.
This
indicates
compound
activity,
was
granted
vitro
vivo
experiments
settle
finding
future.
Язык: Английский
Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis and In Vitro Efficacy
Molecules,
Год журнала:
2025,
Номер
30(1), С. 173 - 173
Опубликована: Янв. 4, 2025
Leishmaniasis,
a
neglected
tropical
disease
caused
by
Leishmania
species,
presents
serious
public
health
challenges
due
to
limited
treatment
options,
toxicity,
high
costs,
and
drug
resistance.
In
this
study,
the
in
vitro
potential
of
malvidin
echioidinin
is
examined
as
antileishmanial
agents
against
L.
amazonensis,
braziliensis,
infantum,
comparing
their
effects
amphotericin
B
(AmpB),
standard
drug.
Malvidin
demonstrated
greater
potency
than
across
all
parasite
stages
species.
Against
malvidin’s
IC50
values
were
197.71
±
17.20
µM
(stationary
amastigotes)
258.07
17
(axenic
amastigotes),
compared
echioidinin’s
272.99
29.90
μM
335.96
19.35
μM.
AmpB
was
more
potent,
with
0.06
0.01
0.10
0.03
µM.
exhibited
lower
cytotoxicity
(CC50:
2920.31
80.29
µM)
(1.06
0.12
favorable
selectivity
index.
It
reduced
infection
rates
35.75%
amazonensis-infected
macrophages.
The
silico
analysis
revealed
strong
binding
between
arginase,
residues
HIS139
PRO258
playing
key
roles.
Gene
expression
indicated
modulation
oxidative
stress
DNA
repair
pathways,
involving
genes
like
GLO1
APEX1.
These
findings
suggest
safe,
natural
compound,
warranting
further
vivo
studies
confirm
its
therapeutic
efficacy
pharmacokinetics
animal
models.
Язык: Английский
The latest progress in assay development in leishmaniasis drug discovery: a review of the available papers on PubMed from the past year
Expert Opinion on Drug Discovery,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 6, 2025
Leishmaniasis
is
a
significant
neglected
tropical
disease
with
limited
treatment
options
that
urgently
requires
ongoing
efforts
in
drug
discovery.
Recent
advances
have
focused
on
the
development
of
new
assays
and
methods
to
identify
effective
therapeutic
candidates.
Язык: Английский
Evaluation of the Antileishmanial Activity of Some Benzimidazole Derivatives Using In Vitro and In Silico Techniques
Veterinary Sciences,
Год журнала:
2025,
Номер
12(6), С. 550 - 550
Опубликована: Июнь 5, 2025
Benzimidazole
derivatives
are
well
known
for
their
anthelmintic
activity.
Investigating
the
potential
efficacy
of
new
this
class
against
various
parasites
is
essential
to
identify
novel
drug
candidates.
For
purpose,
an
in-house
molecular
database
was
screened,
and
four
benzimidazole-based
molecules
were
chosen
evaluate
antiprotozoal
The
compounds
(K1–K4)
had
been
previously
synthesized
through
a
four-step
procedure.
in
vitro
cytotoxic
properties
assessed
Leishmania
(L.)
major
strain
L929
mouse
fibroblast
cells.
tests
indicated
that
K1
(3-Cl
phenyl)
demonstrated
antileishmanial
effect
(IC50
=
0.6787
µg/mL)
cytotoxicity
at
elevated
concentrations
(CC50
250
healthy
These
findings
comparable
those
AmpB.
activity
values
determined
as
follows:
K2;
8.89
µg/mL,
K3;
45.11
K4;
69.19
µg/mL.
CC50
K2,
63
µg/mL;
0.56
K4,
292
Molecular
docking
dynamic
simulations
conducted
elucidate
mechanisms
action
test
substances.
In
silico
investigations
interactions
between
active
site
pteridine
reductase
1
(PTR1),
which
biosynthetic
enzyme
parasite
proliferation.
N-alkyl
exhibit
inhibitory
L.
promastigotes.
Therefore,
these
suggest
vivo
evaluation
warranted,
structural
modifications
may
lead
identification
more
effective
agents.
Язык: Английский
Targeting Leishmania infantum Mannosyl-oligosaccharide glucosidase with natural products: potential pH-dependent inhibition explored through computer-aided drug design
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Май 30, 2024
Visceral
Leishmaniasis
(VL)
is
a
serious
public
health
issue,
documented
in
more
than
ninety
countries,
where
an
estimated
500,000
new
cases
emerge
each
year.
Regardless
of
novel
methodologies,
advancements,
and
experimental
interventions,
therapeutic
limitations,
drug
resistance
are
still
challenging.
For
this
reason,
based
on
previous
research,
we
screened
natural
products
(NP)
from
Nuclei
Bioassays,
Ecophysiology,
Biosynthesis
Natural
Products
Database
(NuBBE
DB)
,
Mexican
Compound
(BIOFACQUIM),
Peruvian
(PeruNPDB)
databases,
addition
to
structural
analogs
Miglitol
Acarbose,
which
have
been
suggested
as
treatments
for
VL
shown
encouraging
action
against
parasite’s
N-glycan
biosynthesis.
Using
computer-aided
design
(CADD)
approaches,
the
potential
inhibitory
effect
these
NP
candidates
was
evaluated
by
inhibiting
Mannosyl-oligosaccharide
Glucosidase
Protein
(MOGS)
Leishmania
infantum
enzyme
essential
protein
glycosylation
process,
at
various
pH
mimic
changing
environment.
Also,
computational
analysis
used
evaluate
Absorption,
Distribution,
Metabolism,
Excretion,
Toxicity
(ADMET)
profile,
while
molecular
dynamic
simulations
were
gather
information
interactions
between
ligands
target.
Our
findings
indicated
that
Ocotillone
Subsessiline
antileishmanial
effects
5
7,
respectively,
due
their
high
binding
affinity
MOGS
active
center.
Furthermore,
compounds
non-toxic
had
be
administered
orally.
This
research
indicates
promising
anti-leishmanial
activity
Subsessiline,
suggesting
further
validation
through
vitro
vivo
experiments.
Язык: Английский
Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis And In Vitro Efficacy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 4, 2024
Abstract
Leishmaniasis
is
a
neglected
tropical
disease,
caused
by
distinct
Leishmania
species,
which
have
significant
public
health
challenges
due
to
treatment
limitations
such
as
toxicity,
high
cost,
and
drug
resistance.
This
study
explores
the
in
vitro
potential
of
Malvidin
Echioidinin
probable
antileishmanial
agents
against
amazonensis
,
L.
braziliensis
infantum
comparing
their
efficacy
Amphotericin
B
(AmpB),
standard
drug.
was
more
potent
than
across
all
parasite
stages
species.
For
Malvidin’s
inhibitory
concentration
(IC
50
)
values
were
197.71±17.20
µM
258.07±17
(stationary
axenic
amastigotes,
respectively);
whereas
revealed
IC
272.99±29.90
μM
335.96±19.35
respectively).
AmpB
showed
0.06±0.01
0.10±0.03
µM,
respectively.
demonstrated
lower
cytotoxicity
activity
mammalian
cells
with
cytotoxic
(CC
value
2,920.31±80.29
while
AmpB’s
1.06±0.12
µM.
also
exhibited
favorable
selectivity
index
(SI)
values.
reduced
infection
rates
up
35.75%
-infected
macrophages.
In
silico
analysis
uncovered
strong
binding
interactions
between
enzyme
arginase
three
key
residues
HIS139
PRO258
playing
crucial
role.
Tissue-specific
markers
expression
highlighted
modulation
genes
involved
oxidative
stress
DNA
repair,
including
glyoxalase
1
(GLO1)
apurinic/apyrimidinic
endodeoxyribonuclease
(APEX1).
The
data
corroborate
hypothesis
that
safe
can
control
parasites
new
natural
compound
for
treatment.
To
further
assess
its
therapeutic
potential,
vivo
studies
are
required
evaluate
efficacy,
safety,
pharmacokinetics
animal
models,
will
be
essential
validating
role
candidate
leishmaniasis
Язык: Английский
TargetingLeishmania infantumMannosyl-oligosaccharide glucosidase with natural products: pH-dependent inhibition explored through computer-aided drug design
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 16, 2024
Abstract
Visceral
Leishmaniasis
(VL)
is
a
serious
public
health
issue,
documented
in
more
than
ninety
countries,
where
an
estimated
500,000
new
cases
emerge
each
year.
Regardless
of
novel
methodologies,
advancements,
and
experimental
interventions,
therapeutic
limitations,
drug
resistance
are
still
challenging.
For
this
reason,
based
on
previous
research,
we
screened
natural
products
(NP)
from
Nuclei
Bioassays,
Ecophysiology,
Biosynthesis
Natural
Products
Database
(NuBBEDB),
Mexican
Compound
(BIOFACQUIM),
Peruvian
(PeruNPDB)
databases,
addition
to
structural
analogs
Miglitol
Acarbose,
which
have
been
suggested
as
treatments
for
VL
shown
encouraging
action
against
parasite’s
N-glycan
biosynthesis.
Using
computer-aided
design
(CADD)
approaches,
the
inhibitory
effect
these
NP
candidates
was
evaluated
by
inhibiting
Mannosyl-oligosaccharide
Glucosidase
Protein
(MOGS)
Leishmania
infantum
,
enzyme
essential
protein
glycosylation
process,
at
various
pH
mimic
changing
environment.
Also,
computational
analysis
used
evaluate
Absorption,
Distribution,
Metabolism,
Excretion,
Toxicity
(ADMET)
profile,
while
molecular
dynamic
simulations
were
gather
information
interactions
between
ligands
target.
Our
findings
indicated
that
Ocotillone
Subsessiline
potential
antileishmanial
effects
5
7,
respectively,
due
their
high
binding
affinity
MOGS
active
center.
Furthermore,
compounds
non-toxic
had
be
administered
orally.
This
research
indicates
promising
anti-leishmanial
activity
Subsessiline,
suggesting
further
validation
through
vitro
vivo
experiments.
Язык: Английский
Targeting with structural analogs of natural products the purine salvage pathway inLeishmania (Leishmania) infantumby computer-aided drug design approaches
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 29, 2023
Abstract
Visceral
Leishmaniasis
(VL)
has
a
high
death
rate
with
500,000
new
cases
and
50,000
deaths
occurring
annually.
Despite
the
development
of
novel
strategies
technologies,
there
is
no
adequate
treatment
for
disease.
Therefore,
purpose
this
study
to
find
structural
analogs
natural
products
as
potential
drugs
treat
VL.
To
choose
from
that
have
demonstrated
anti-leishmanial
anti-adenine
phosphoribosyltransferase
(APRT)
properties,
might
bind
several
targets
purine
salvage
pathway,
we
used
computer-aided
drug
design
(CADD)
techniques.
Computational
techniques
were
pathway
Leishmania
infantum
,
molecular
dynamic
simulations
gather
information
on
interactions
between
ligands
proteins.
An
analog
alkaloid
Skimmianine,
N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide,
good
binding
affinity
two
L.
targets,
expected
toxicity,
oral
route
administration.
This
indicates
compounds
may
activity,
which
granted
in
vitro
vivo
experiments
settle
finding
future.
Язык: Английский