Pharmacology Research & Perspectives,
Год журнала:
2025,
Номер
13(2)
Опубликована: Март 24, 2025
The
research
and
design
of
new
inhibitors
for
the
treatment
diseases
such
as
Alzheimer's
disease
glaucoma
through
inhibition
cholinesterases
(ChEs;
acetylcholinesterase,
AChE
butyrylcholinesterase,
BChE)
carbonic
anhydrase
enzymes
are
among
important
targets.
Here,
a
series
novel
sulfonamide-bearing
pyrazolone
derivatives
(1a-f
2a-f)
were
successfully
synthesized
characterized
by
using
spectroscopic
analytical
methods.
inhibitory
activities
these
newly
compounds
evaluated
both
in
vitro
silico
their
effect
on
anhydrases
(hCA
I
hCA
II
isoenzymes)
ChEs.
studies
showed
that
demonstrated
potential
activity,
with
KI
values
covering
following
ranges:
18.03
±
2.86-75.54
4.91
nM
I,
24.84
1.57-85.42
6.60
II,
7.45
0.98-16.04
1.60
AChE,
34.78
5.88-135.70
17.39
BChE.
Additionally,
many
promising
some
higher
potency
than
reference
compounds.
While
have
also
identified
binding
positions
compounds,
crystal
structures
BChE
receptors.
varying
affinities
designed
ChEs
isoenzymes
show
could
hold
promise
alternative
agents
selectively
inhibiting
hCAs
glaucoma.
Biotechnology and Applied Biochemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
Diabetes
mellitus,
especially
type
2,
is
a
global
health
challenge,
and
effective
enzyme
inhibitors
are
essential
for
its
control.
Conventional
have
drawbacks
such
as
gastrointestinal
side
effects
regional
availability,
examples
being
acarbose
epalrestat.
Moreover,
tyrosinase,
which
controls
melanin
synthesis
also
target
reducing
hyperpigmentation
disorders.
In
this
study,
we
demonstrate
the
inhibitory
action
of
novel
isoindole-1,3-dione-based
sulfonamides
against
key
enzymes
associated
with
diabetes
hyperpigmentation,
α-Glucosidase
(α-Glu),
aldose
reductase
(ALR2),
tyrosinase.
The
presynthesized
compounds
(3,
4a-k)
tested
in
vitro
inhibition
α-Glu,
ALR2,
tyrosinase
compared
reference
acarbose,
epalrestat,
kojic
acid.
Kinetic
studies
showed
that
both
competitive
noncompetitive
modes
were
observed.
Among
them,
compound
4a
displayed
highest
ALR2
potency
(Ki:
0.211
µM)
was
superior
to
terms
4k
shown
be
more
potent
Ki
0.049
µM,
particularly
versus
acarbose.
Compound
4d
excellent
activity
1.43
assays,
much
than
Molecular
docking
revealed
details
enzyme-binding
interactions,
justify
respective
mechanisms
Structure-activity
relationships
reflected
strong
hydrogen
bonding
hydrophobic
interactions
led
higher
potency.
These
findings
highlight
importance
therapeutic
agents
will
provide
valuable
leads
developing
multifunctional
diabetic
complications
hyperpigmentation.
Biotechnology and Applied Biochemistry,
Год журнала:
2024,
Номер
71(5), С. 1079 - 1093
Опубликована: Май 7, 2024
The
identification
of
novel
acetylcholinesterase
inhibitors
holds
significant
relevance
in
the
treatment
Alzheimer's
disease
(AD),
prevailing
form
dementia.
exploration
alternative
to
conventional
is
steadily
gaining
prominence.
Quinones,
categorized
as
plant
metabolites,
represent
a
specific
class
compounds.
In
this
study,
inhibitory
effects
various
naphthoquinone
derivatives,
along
with
anthraquinone
and
its
on
(AChE)
enzyme
were
investigated
for
purpose.
An
vitro
investigation
was
conducted
examine
these
compounds
order
clarify
possible
mechanism
inhibition
interaction
between
chemicals.
addition,
an
silico
carried
out
understand
conceivable
inhibitor
binding
process
enzyme's
active
site.
acquired
outcomes
corroborated
results.
AChE
found
be
effectively
inhibited
by
both
naphthoquinones
anthraquinones,
constant
(K
Archiv der Pharmazie,
Год журнала:
2023,
Номер
357(2)
Опубликована: Ноя. 16, 2023
Abstract
In
this
study,
the
mechanisms
by
which
enzymes
glucose‐6‐phosphate
dehydrogenase
(G6PD),
6‐phosphogluconate
(6PGD),
glutathione
reductase
(GR),
glutathione‐S‐transferase
(GST),
and
thioredoxin
(TrxR)
are
inhibited
methotrexate
(MTX)
were
investigated,
as
well
whether
antioxidant
morin
can
mitigate
or
prevent
these
adverse
effects
in
vivo
silico.
For
10
days,
rats
received
oral
doses
of
(50
100
mg/kg
body
weight).
On
fifth
day,
a
single
intraperitoneal
injection
MTX
(20
weight)
was
administered
to
generate
toxicity.
Decreased
activities
G6PD,
6PGD,
GR,
GST,
TrxR
associated
with
MTX‐related
toxicity
while
treatment
increased
activity
enzymes.
The
docking
analysis
indicated
that
H‐bonds,
pi–pi
stacking,
pi–cation
interactions
dominant
enzyme‐binding
pockets.
Furthermore,
docked
poses
against
GST
subjected
molecular
dynamic
simulations
for
200
ns,
assess
stability
both
complexes
also
predict
key
amino
acid
residues
binding
pockets
throughout
simulation.
results
study
suggest
may
be
viable
means
alleviating
enzyme
important
regulatory
MTX‐induced
Journal of Molecular Recognition,
Год журнала:
2024,
Номер
37(3)
Опубликована: Март 21, 2024
Abstract
Glucose‐6‐phosphate
dehydrogenase
(G6PD)
and
6‐phosphogluconate
(6PGD)
are
pentose
phosphate
pathway
enzymes.
Compounds
with
a
heterocyclic
pyrrole
ring
system
containing
this
atom
can
be
derivatized
various
functional
groups
into
highly
effective
bioactive
agents.
In
study,
derivatives
on
these
enzyme's
activity
were
investigated.
The
IC
50
values
of
different
concentrations
for
G6PD
found
in
the
range
0.022–0.221
mM
K
i
0.021
±
0.003–0.177
6PGD
0.020–0.147,
0.013
0.002–0.113
0.030
mM.
2‐acetyl‐1‐methylpyrrole
(
1g
)
showed
best
inhibition
value
addition,
silico
molecular
docking
experiments
performed
to
elucidate
how
1a
–
g
interact
binding
sites
target
study's
findings
could
used
create
innovative
therapeutics
that
treatment
many
diseases,
especially
cancer
manifestations.
