ChemistrySelect,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Jan. 2, 2023
Abstract
Heterocycles
are
a
privileged
motif
that
appears
as
momentous
objective
in
medicinal
chemistry.
An
important
class
of
compounds
for
drug
discovery
and
design
is
indole
its
derivatives,
which
have
been
examined
variety
biological
activities.
Therefore,
it
noteworthy
the
modern
progress
synthetic,
chemistry;
last
decade
has
onlooker
with
multitude
reports
on
several
derivatives
corroborating
these
chemical
entities
to
be
renowned
target
new
drugs.
The
current
study
includes
brief
natural
sources
indole,
range
commercially
available
indole‐based
Additionally,
this
review
discusses
numerous
facets
structure‐activity
relationship
(SARs)
provides
information
about
varied
pharmacological
effects
derivatives.
literature
data
presented
anti‐pharmacological
agents
herein
covers
largely
from
year
2015
mid
2022.
Molecules,
Journal Year:
2024,
Volume and Issue:
29(9), P. 2127 - 2127
Published: May 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.
Molecules,
Journal Year:
2024,
Volume and Issue:
29(19), P. 4770 - 4770
Published: Oct. 9, 2024
Indole
derivatives
have
become
an
important
class
of
compounds
in
medicinal
chemistry,
recognized
for
their
wide-ranging
biological
activities
and
therapeutic
potential.
This
review
provides
a
comprehensive
overview
recent
advances
the
evaluation
indole-based
last
five
years,
highlighting
roles
cancer
treatment,
infectious
disease
management,
anti-inflammatory
therapies,
metabolic
disorder
interventions,
neurodegenerative
management.
shown
significant
efficacy
targeting
diverse
pathways,
making
them
valuable
scaffolds
designing
new
drugs.
Notably,
these
demonstrated
ability
to
combat
drug-resistant
cells
pathogens,
breakthrough
field,
offer
promising
options
chronic
diseases
such
as
diabetes
hypertension.
By
summarizing
key
findings
exploring
underlying
mechanisms,
this
underscores
potential
indole
addressing
major
healthcare
challenges,
thereby
instilling
hope
optimism
field
modern
medicine.
Neurology International,
Journal Year:
2025,
Volume and Issue:
17(2), P. 26 - 26
Published: Feb. 7, 2025
Alzheimer’s
and
Parkinson’s
are
the
most
common
neurodegenerative
diseases
(NDDs).
The
development
of
aberrant
protein
aggregates
progressive
permanent
loss
neurons
major
characteristic
features
these
disorders.
Although
precise
mechanisms
causing
disease
(AD)
(PD)
still
unknown,
there
is
a
wealth
evidence
suggesting
that
misfolded
proteins,
accumulation
dysfunction
neuroreceptors
mitochondria,
dysregulation
enzymes,
release
neurotransmitters
significantly
influence
pathophysiology
diseases.
There
no
effective
protective
medicine
or
therapy
available
even
with
availability
numerous
medications.
an
urgent
need
to
create
new
powerful
bioactive
compounds
since
number
people
NDDs
rising
globally.
Heterocyclic
have
consistently
played
pivotal
role
in
drug
discovery
due
their
exceptional
pharmaceutical
properties.
Many
clinically
approved
drugs,
such
as
galantamine
hydrobromide,
donepezil
hydrochloride,
memantine
opicapone,
feature
heterocyclic
cores.
As
therapeutic
potential,
heterocycles
intriguing
research
topic
for
drugs
PD
AD.
This
review
aims
provide
current
insights
into
potential
use
targeting
diverse
targets
manage
potentially
treat
patients
AD
PD.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: Feb. 20, 2023
Alzheimer's
disease
(AD),
a
persistent
neurological
dysfunction,
has
an
increasing
prevalence
with
the
aging
of
world
and
seriously
threatens
health
elderly.
Although
there
is
currently
no
effective
treatment
for
AD,
researchers
have
not
given
up,
are
committed
to
exploring
pathogenesis
AD
possible
therapeutic
drugs.
Natural
products
attracted
considerable
attention
owing
their
unique
advantages.
One
molecule
can
interact
multiple
AD-related
targets,
thus
having
potential
be
developed
in
multi-target
drug.
In
addition,
they
amenable
structural
modifications
increase
interaction
decrease
toxicity.
Therefore,
natural
derivatives
that
ameliorate
pathological
changes
should
intensively
extensively
studied.
This
review
mainly
presents
research
on
AD.
Archiv der Pharmazie,
Journal Year:
2023,
Volume and Issue:
357(1)
Published: Nov. 8, 2023
Abstract
Dementia
is
a
cognitive
disturbance
that
generally
correlated
with
central
nervous
system
diseases,
especially
Alzheimer's
disease.
The
limited
number
of
medications
available
insufficient
to
improve
the
lifestyle
patients
suffering
from
this
Thus,
new
benzimidazole–thiazole
hybrids
(
3–10
)
were
designed
and
synthesized
as
acetylcholinesterase
(AChE)
butyrylcholinesterase
(BChE)
inhibitory
agents.
in
vitro
evaluation
displayed
derivatives
4b
,
4d
5b
6a
7a
8b
demonstrated
dual
efficiency
against
both
AChE
IC
50
ranging
4.55
8.62
µM
BChE
3.50
8.32
µM.
By
analyzing
Lineweaver–Burk
plot,
an
uncompetitive
form
inhibition
was
determined
for
highly
active
compound
revealing
its
type.
human
telomerase
reverse
transcriptase‐immortalized
retinal
pigment
epithelial
cell
line
used
ensure
safety
most
potent
cholinesterase
inhibitors.
Furthermore,
compounds
evaluated
their
neuroprotective
antioxidant
properties,
well
ability
suppress
COX‐2.
results
presented
significant
neuroprotection
H
2
O
‐induced
damage
SH‐SY5Y
cells
%
viability
67.42
±
7.90%,
62.51
6.71%,
72.61
8.10%,
respectively,
while
tested
candidates
did
not
reveal
activity.
Otherwise,
outstanding
COX‐2
effects
0.050
0.080
μM
relative
celecoxib
(IC
=
µM).
In
addition,
molecular
docking
carried
out
sites
(PDB
ID:
4EY7)
code:
1P0P).
fit
portions,
scores
−8.65
−6.64
kcal/mol
(for
AChE)
−8.71
−7.73
BChE).
silico
show
have
good
physicochemical
pharmacokinetic
properties
no
Lipinski
rule
violations.
preceding
exhibited
could
be
template
developing
more
inhibitors
future.
Future Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
15(6), P. 473 - 495
Published: March 1, 2023
Background:
Alzheimer's
disease
is
a
neurological
disorder
that
causes
brain
cells
to
shrink
and
die.
Aim:
Thirteen
novel
'oxathiolanyl',
'pyrazolyl'
'pyrimidinyl'
indole
derivatives
were
designed
synthesized
as
anti-Alzheimer's
treatment.
Method:In
vitro
enzyme
assay
was
performed
against
both
AChE
BChE
enzymes.
In
addition,
antioxidant
cytotoxicity
on
normal
cell
line
determined.
Molecular
docking
dynamic
simulations
conducted
confirm
the
binding
mode
in
esterases'
active
sites.
silico
absorption,
distribution,
metabolism,
excretion
toxicity
studies
also
carried
out.
Results
&
conclusion:
Compounds
5,
7
11
exhibited
superior
inhibitory
activity
acetylcholinesterase
butyrylcholinesterase,
with
IC50
values
of
0.042
3.003
μM,
2.54
0.207
μM
0.052
2.529
respectively,
compared
donepezil.
Drug Development Research,
Journal Year:
2023,
Volume and Issue:
84(8), P. 1578 - 1594
Published: Sept. 7, 2023
Abstract
Alzheimer's
disease
(AD)
is
a
chronic
and
irreversible
neurodegenerative
associated
with
aging.
It
characterized
by
the
progressive
loss
of
memory
other
cognitive
functions.
Although
exact
etiology
AD
not
well
explored,
several
factors,
such
as
deposition
amyloid‐β
(Aβ)
plaques,
hyperphosphorylation
tau
protein,
presence
low
levels
acetylcholine,
generation
oxidative
stress,
are
key
mediators
in
progression
AD.
Currently,
clinical
treatment
options
for
limited
based
on
cholinesterase
(ChE)
inhibitors
(e.g.,
donepezil,
rivastigmine,
galantamine),
N
‐methyl‐
d
‐aspartic
acid
receptor
antagonists
memantine),
recently
approved
Aβ
modulator
aducanumab).
Tryptamine
(2‐(1
H
‐indol‐3‐yl)ethan‐1‐amine)
small
molecule
that
contains
an
indole
nucleus
ethylamine
side
chain.
also
active
metabolite
tryptophan.
possesses
wide
range
biological
activities
related
to
disorders,
ChE
inhibition,
aggregation
antioxidant
effects,
monoamine‐oxidase
neuroprotection.
Several
tryptamine‐based
hybrid
analogs
currently
being
investigated
multifunctional
agents
development
novel
hybrids
treatment.
Thus,
this
review
article
aims
provide
in‐depth
insights
into
research
progress
strategies
designing
used
therapy.
