ACS Omega,
Год журнала:
2022,
Номер
7(49), С. 45036 - 45044
Опубликована: Ноя. 30, 2022
Head
and
neck
squamous
cell
carcinoma
(HNSCC)
is
the
sixth
most
prevalent
cancer
in
world
of
developing
countries.
Increased
disease
burden
a
smaller
number
approved
targeted
therapies
are
growing
concern
worldwide.
Isoindolinone
motifs
have
been
central
part
many
pharmacological
compounds,
their
derivatives
possess
substantial
anticancer
potential.
However,
potential
against
HNSCC
has
not
well
investigated.
In
current
study,
series
3-methyleneisoindolinones
designed
synthesized
late-stage
intramolecular
Heck
cyclization
was
achieved
to
evaluate
cells.
Additionally,
silico
ADME
profiling
compounds
revealed
drug-likeness
properties
as
drug
candidates.
Among
3-bromo-5-methylpyridin-2-yl-3-methyleneisoindolin-1-one,
i.e.,
3n,
with
pyridyl
unit
exhibited
significant
cytotoxicity
The
cytotoxic
varied
depending
on
nature
substituents
present
established
structure-activity
relationship
studies.
Further,
flow
cytometric
analysis
showed
that
3f,
3h,
3n
triggered
intracellular
oxidative
stress,
disrupted
mitochondrial
membrane
potential,
interrupted
cycle
cells
S-phase
sub-G1
phase.
also
pro-apoptotic
induced
cellular
apoptosis
Overall,
findings
this
study
attributed
3-methyleneisoindolinone
chemistry
efficacy
evaluation
corroborated
HNSCC.
It
will
pave
way
further
design
optimize
novel
effective
antitumor
agents,
which
may
provide
treatment
modalities
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,
Год журнала:
2021,
Номер
26(21), С. 6573 - 6573
Опубликована: Окт. 30, 2021
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
and
the
leading
cause
of
dementia
worldwide.
The
limited
pharmacological
approaches
based
on
cholinesterase
inhibitors
only
provide
symptomatic
relief
to
AD
patients.
Moreover,
adverse
side
effects
such
as
nausea,
vomiting,
loss
appetite,
muscle
cramps,
headaches
associated
with
these
drugs
numerous
clinical
trial
failures
present
substantial
limitations
use
medications
call
for
detailed
insight
heterogeneity
development
preventive
multifactorial
therapeutic
strategies
urgent
basis.
In
this
context,
we
herein
report
series
quinoline-thiosemicarbazone
hybrid
therapeutics
selective
potent
cholinesterases.
A
facile
multistep
synthetic
approach
was
utilized
generate
target
structures
bearing
multiple
sites
chemical
modifications
establishing
drug-receptor
interactions.
all
synthesized
compounds
were
fully
established
using
readily
available
spectroscopic
techniques
(FTIR,
1H-
13C-NMR).
vitro
inhibitory
results
revealed
compound
5b
promising
lead
inhibitor
an
IC50
value
0.12
±
0.02
μM,
5-fold
higher
potency
than
standard
drug
(galantamine;
=
0.62
0.01
μM).
synergistic
effect
electron-rich
(methoxy)
group
ethylmorpholine
moiety
in
conjugates
contributes
significantly
improving
inhibition
level.
Molecular
docking
analysis
various
vital
interactions
amino
acid
residues
reinforced
results.
Kinetics
experiments
competitive
mode
while
ADME
properties
favored
translation
identified
into
safe
candidates
pre-clinical
testing.
Collectively,
activity
data
from
key
physicochemical
merit
further
research
ensure
design
high-quality
disease.
International Journal of Applied Pharmaceutics,
Год журнала:
2025,
Номер
unknown, С. 23 - 38
Опубликована: Янв. 7, 2025
Prostate
cancer
is
one
of
the
leading
causes
male
death
globally,
and
its
overall
incidence
flaunts
a
rising
trend
over
years.
Currently
available
treatment
modalities
for
prostate
suffer
from
severe
toxicity,
unpredictable
efficacy,
high
costs,
emergence
resistance
towards
anti-cancer
compounds.
This
substantiates
need
to
develop
novel
potent
anti-proliferative
agents
against
cancer.
Multiple
cellular
mechanisms
underlie
development
and,
thus,
multiple
drug
gable
targets.
In
recent
years,
researchers
have
been
conducting
myriad
investigations
in
this
direction.
work
recapitulates
synthesis
78
such
molecules
based
on
references.
These
compounds
are
classified
tabulated
according
moiety
that
they
possess.
Further,
review
study
highlights
member
each
chemical
class.
addition,
provides
fundamental
insights
into
design
through
structure-activity
relationship
series
compounds,
thereby
unlocking
new
doors
future
exploration.
Antioxidants,
Год журнала:
2020,
Номер
9(1), С. 55 - 55
Опубликована: Янв. 8, 2020
Selenium
compounds
are
pivotal
in
medicinal
chemistry
for
their
antitumoral
and
antioxidant
properties.
Forty
seven
acylselenoureas
have
been
designed
synthesized
following
a
fragment-based
approach.
Different
scaffolds,
including
carbo-
hetero-cycles,
along
with
mono-
bi-cyclic
moieties,
linked
to
the
selenium
containing
skeleton.
The
dose-
time-dependent
radical
scavenging
activity
all
of
were
assessed
using
vitro
2,2-diphenyl-1-picrylhydrazyl
(DPPH)
2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic
acid)
(ABTS)
assays.
Some
them
showed
greater
capacity
at
low
doses
shorter
times
than
ascorbic
acid.
Therefore,
four
evaluated
test
protective
effects
against
H2O2-induced
oxidative
stress.
One
derivative
protected
cells
damage,
increasing
cell
survival
by
up
3.6-fold.
Additionally,
cytotoxic
was
screened
several
cancer
cells.
Eight
selected
determine
half
maximal
inhibitory
concentration
(IC50)
values
towards
breast
lung
cells,
selectivity
indexes.
turned
out
be
much
more
sensitive
lung.
Two
(5d
10a)
stood
IC50
between
4.2
μM
8.0
MCF-7
T47D
indexes
22.9.
In
addition,
compound
10b
exhibited
dual
activities.
Although
further
evidence
is
needed,
acylselenourea
scaffold
could
feasible
frame
develop
new
agents.
