Archiv der Pharmazie,
Год журнала:
2024,
Номер
358(1)
Опубликована: Дек. 27, 2024
Alzheimer's
disease
(AD)
is
a
prevalent
neurological
illness
that
affects
over
80%
of
aged
adults
globally
in
cases
dementia.
Although
the
exact
pathophysiological
causes
AD
remain
unclear,
its
pathogenesis
primarily
driven
by
several
distinct
biochemical
alterations:
(i)
accumulation
toxic
Aβ
plaques,
(ii)
hyperphosphorylation
tau
proteins,
(iii)
oxidative
stress
resulting
cell
death,
and
(iv)
an
imbalance
between
two
main
neurotransmitters,
glutamate
acetylcholine
(ACh).
Currently,
there
are
very
few
medications
available
no
treatment.
Presently
marketed
include
memantine,
N-methyl-d-aspartate
receptor
(NMDA)
antagonist,
acetylcholinesterase
(AChE)
inhibitors:
rivastigmine,
donepezil,
galantamine.
Unfortunately,
these
only
useful
initial
stages
AD.
The
mentioned
provide
symptomatic
relief
do
not
slow
down
progression
advanced
stages.
Therefore,
urgent
need
to
develop
potential
candidates
treat
AD,
symptomatically
therapeutically.
Many
research
groups
focus
on
natural
products
due
their
diverse
therapeutic
profiles
easy
availability.
One
such
product
deoxyvasicinone,
isolated
from
Adhatoda
vasica.
Given
broad
pharmacological
profile,
various
researchers
have
developed
semisynthetic
hybrids
deoxyvasicinone
address
multifaceted
diseases
like
In
this
review
article,
we
tried
summarize
past
decade
(2014-2024)
for
managing
We
design,
activity,
structure-activity
relationship
(SAR)
analysis.
hope
enhances
reader's
understanding
future
exploratory
options
management.
Molecules,
Год журнала:
2024,
Номер
29(9), С. 2127 - 2127
Опубликована: Май 3, 2024
Neurodegeneration
is
a
gradual
decay
process
leading
to
the
depletion
of
neurons
in
both
central
and
peripheral
nervous
systems,
ultimately
resulting
cognitive
dysfunctions
deterioration
brain
functions,
alongside
decline
motor
skills
behavioral
capabilities.
Neurodegenerative
disorders
(NDs)
impose
substantial
socio-economic
strain
on
society,
aggravated
by
advancing
age
world
population
absence
effective
remedies,
predicting
negative
future.
In
this
context,
urgency
discovering
viable
therapies
critical
and,
despite
significant
efforts
medicinal
chemists
developing
potential
drug
candidates
exploring
various
small
molecules
as
therapeutics,
regrettably,
truly
treatment
yet
be
found.
Nitrogen
heterocyclic
compounds,
particularly
those
containing
indole
nucleus,
which
has
emerged
privileged
scaffold,
have
attracted
particular
attention
for
variety
pharmacological
applications.
This
review
analyzes
rational
design
strategy
adopted
different
research
groups
development
anti-neurodegenerative
indole-based
compounds
modulate
molecular
targets
involved
NDs,
with
reference
most
recent
advances
between
2018
2023.
Abstract
Skeletal
editing
comprises
the
structural
reorganization
of
compounds.
Such
can
be
achieved
through
atom
swapping,
insertion,
deletion
or
compound’s
backbone
structure
1,2
.
Conducted
at
a
late
stage
in
drug
development
campaigns,
skeletal
enables
diversification
an
existing
pharmacophore,
enhancing
efficiency
development.
Instead
constructing
heteroarene
classically
from
basic
building
blocks,
variants
are
readily
accessible
directly
starting
lead
compound
approved
pharmacophore.
Here
we
present
C
to
N
swapping
indoles
C2
position
give
indazoles
oxidative
cleavage
indole
core
and
subsequent
ring
closure.
Reactions
proceed
ring-opened
oximes
as
intermediates.
These
deconstructed
intermediates
also
diverted
into
benzimidazoles
resulting
overall
with
concomitant
reorganization.
The
same
diverting
strategies
equally
well
applicable
benzofurans
leading
either
benzisoxazoles
benzoxazoles.
classes
obtained
these
methods—indazoles
3,4
,
5
6,7
benzoxazoles
8
—are
biologically
relevant
moieties
found
substructures
natural
products
pharmaceuticals.
procedures
introduced
substantially
enlarge
methods
portfolio
emerging
field
editing.
β-Sultams
are
recognized
as
potential
antibacterial
agents
and
crucial
building
blocks
in
chemical
synthesis.
Herein,
a
"SuFEx
on
silica
gel"
approach
has
been
developed
for
one-step
synthesis
of
β-sultams
utilizing
readily
available
amines
ethenesulfonyl
fluoride
(ESF).
This
process
involves
sequential
Michael
addition
to
ESF,
followed
by
an
intramolecular
SuFEx
reaction
promoted
gel.
Silica
gel
facilitates
the
activation
sulfonyl
through
hydrogen
bonding
between
SVI-F
surface
hydroxyl
groups
eliminates
HF
formed
during
reaction.
Notably,
use
base,
which
is
typically
required
nearly
all
known
reactions,
was
rendered
unnecessary.
The
β-sultam
moiety
successfully
incorporated
into
26
tested
primary
amines,
including
pharmaceuticals
natural
products,
high
yields,
showcasing
broad
applications
this
method.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Июнь 13, 2024
Abstract
This
cross-sectional
study
investigated
differences
in
the
plasma
metabolome
two
groups
of
adults
that
were
similar
age
but
varied
markedly
body
composition
and
dietary
physical
activity
patterns.
Study
participants
included
52
lifestyle
group
(LIFE)
(28
males,
24
females)
control
(CON)
(27
25
females).
The
results
using
an
extensive
untargeted
ultra
high-performance
liquid
chromatography-high
resolution
mass
spectrometry
(UHPLC-HRMS)
metabolomics
analysis
with
10,535
metabolite
peaks
identified
486
important
metabolites
(variable
influence
on
projections
scores
VIP
≥
1)
16
significantly
enriched
metabolic
pathways
differentiated
LIFE
CON
groups.
A
novel
signature
positive
habits
emerged
from
this
highlighted
by
lower
levels
numerous
bile
acids,
amino
acid
profile
characterized
higher
histidine
glutamic
acid,
glutamine,
β-alanine,
phenylalanine,
tyrosine,
proline,
elevated
vitamin
D
status,
beneficial
fatty
acids
gut
microbiome
catabolism
plant
substrates,
reduced
N-glycan
degradation
environmental
contaminants.
established
is
strongly
associated
habits.
robust
consistent
improved
life
expectancy
a
risk
for
chronic
disease.
Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
104(4)
Опубликована: Окт. 1, 2024
ABSTRACT
Alzheimer's
disease
(AD)
is
a
chronic
progressive,
age‐related
neurodegenerative
brain
disorder
characterized
by
the
irreversible
decline
of
memory
and
other
cognitive
functions.
It
one
major
health
threat
21st
century,
which
affects
around
60%
population
over
age
60
years.
The
problem
this
even
more
because
existing
pharmacotherapies
only
provide
symptomatic
relief
without
addressing
basic
factors
disease.
extracellular
deposition
amyloid
β
(Aβ)
to
form
senile
plaques,
intracellular
hyperphosphorylation
tau
neurofibrillary
tangles
(NFTs).
Due
complex
pathophysiology
disease,
various
hypotheses
have
been
proposed,
including
cholinergic,
Aβ,
tau,
oxidative
stress,
metal–ion
hypothesis.
Among
these,
cholinergic
Aβ
are
primary
targets
for
AD.
Therefore,
continuous
advances
made
in
developing
potential
cholinesterase
inhibitors
N
‐methyl‐D‐aspartate
(NMDA)
receptor
antagonists
delay
progression
restore
neurotransmission.
In
review
article,
we
tried
comprehensively
summarize
recent
advancement
NMDA
antagonist
(memantine)
their
hybrid
analogs
as
disease‐modifying
agents
treatment
Furthermore,
also
depicted
design,
rationale,
SAR
analysis
memantine‐based
hybrids
used
last
decade
