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.
Journal of Molecular Recognition,
Год журнала:
2023,
Номер
36(12)
Опубликована: Окт. 8, 2023
Abstract
Enzyme
inhibition
is
a
commonly
utilized
method
for
controlling
enzymatic
activity
in
various
physiologically
relevant
biological
systems.
Herein,
the
selected
five
active
antiviral
drugs,
abacavir,
emtricitabine,
lamivudine,
ribavirin,
and
ritonavir,
were
assayed
as
inhibitors
of
two
human
isoforms
metalloenzyme
carbonic
anhydrase
(
h
CA,
EC
4.2.1.1)
involved
physiological/pathological
conditions.
For
this
aim,
vitro
silico
studies
performed
to
gain
insights
into
plausible
binding
interactions
affinities
drugs
within
CA
I
II
isoforms'
sites.
The
I,
an
isoform
some
pathological
conditions
such
retinal
or
cerebral
edema,
was
moderately
inhibited
by
these
at
micromolar
concentrations
with
K
s
spanning
from
0.49
±
0.05
3.51
0.37
μM
compared
reference
drug
acetazolamide
(AAZ,
0.19
0.01
μM).
Moreover,
II,
promising
target
glaucoma,
epilepsy,
altitude
sickness,
reasonably
agents,
range
0.64
0.08–5.80
AAZ
0.17
Both
results
demonstrated
significant
between
CAs
that
they
can
support
therapeutic
targets
against
above‐mentioned
Additionally,
obtained
will
help
optimize
clinical
dosage
regimens
avoid
drug–drug
unexpectedly
when
used
combination
other
agents.
New Journal of Chemistry,
Год журнала:
2024,
Номер
48(24), С. 10979 - 10989
Опубликована: Янв. 1, 2024
Investigating
innovative
frameworks
for
addressing
Alzheimer's
disease
is
a
challenging
goal.
In
this
specific
scenario,
selection
of
asymmetric
biscarbothioamide
derivatives
(3a–l)
with
different
substitutions
has
been
carefully
formulated
and
successfully
synthesized.
European Journal of Medicinal Chemistry Reports,
Год журнала:
2024,
Номер
10, С. 100131 - 100131
Опубликована: Янв. 18, 2024
The
emergence
of
tumor-associated
human
carbonic
anhydrases
(hCA)
as
promising
therapeutic
targets
has
urged
rigorous
research
into
the
development
potent
and
selective
hCA
IX
XII
inhibitors.
Rationalization
targeting
tumor-specific
isoforms
is
a
major
challenge
that
requires
comprehensive
understanding
interactions
between
inhibitors
dynamic
active
site.
benzenesulfonamides
its
bioisosteres
are
currently
being
used
clinically
various
through
classical
inhibitory
mechanism.
In
addition,
several
other
chemotypes
have
also
been
developed
with
improved
potency
selectivity
non-classical
mechanisms.
Coumarin
derivatives
represent
highly
XII.
Recently,
pharmacophores
were
proven
to
strong
against
including
pyrazole,
1,2,3-triazole,
4-thiazolidinone,
thiourea.
This
review
navigates
role
in
cancer
biology,
encompassing
different
inhibition
approaches,
strategic
design
methodologies,
recent
advancements
rational
inhibitors,
exploration
structure-activity
relationships,
in-depth
mechanistic
insights,
PET
imaging
applications
for
vivo
visualization
target
enzymes.
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2024,
Номер
38(4)
Опубликована: Апрель 1, 2024
Abstract
Doxorubicin
(DOX)
is
widely
used
in
cancer
treatment
but
the
dose‐related
toxicity
of
DOX
on
organs
including
liver
limit
its
use.
Therefore,
there
great
interest
combining
with
natural
compounds
antioxidant
properties
to
reduce
and
increase
drug
efficacy.
Esculetin
a
coumarin
derivative
biological
encompassing
anti‐inflammatory
activities.
In
light
these
properties,
this
study
was
meticulously
crafted
investigate
potential
esculetin
preventing
doxorubicin
(DOX)‐induced
hepatotoxicity
Sprague‐Dawley
rats.
The
rats
were
divided
into
total
six
groups:
control
group,
group
(administered
at
cumulative
dose
5
mg/kg
intraperitoneally
every
other
day
for
2
weeks),
E50
50
day),
E100
100
day)
combined
groups
(DOX
+
E100)
which
administered
together
DOX.
treatments,
both
alone
combination
E50,
manifested
reduction
catalase
(CAT
mRNA)
levels
comparison
group.
Notably,
enzymatic
activities
superoxide
dismutase
(SOD),
CAT,
glutathione
peroxidase
(GPx)
witnessed
significant
decreases
treated
Moreover,
induced
statistically
elevation
malondialdehyde
(MDA)
levels,
coupled
concurrent
decrease
(GSH)
levels.
Additionally,
molecular
docking
studies
conducted.
However,
further
are
needed
confirm
hepatoprotective
precisely
elucidate
mechanisms
action.
