Multi- and poly-pharmacology of carbonic anhydrase inhibitors
Pharmacological Reviews,
Год журнала:
2024,
Номер
77(1), С. 100004 - 100004
Опубликована: Сен. 26, 2024
Eight
genetically
distinct
families
of
the
enzyme
carbonic
anhydrase
(CA,
EC
4.2.1.1)
have
been
described
in
organisms
overall
phylogenetic
tree.
They
catalyze
hydration
CO2
to
bicarbonate
and
protons
are
involved
pH
regulation,
chemosensing,
metabolism.
The
15
α-CA
isoforms
present
humans
pharmacological
drug
targets
known
for
decades,
their
inhibitors
being
used
as
diuretics,
antiglaucoma,
antiepileptic,
or
antiobesity
drugs,
well
management
acute
mountain
sickness,
idiopathic
intracranial
hypertension,
recently,
antitumor
theragnostic
agents.
Other
potential
applications
include
use
CA
(CAIs)
inflammatory
conditions,
cerebral
ischemia,
neuropathic
pain,
Alzheimer/Parkinson
disease
management.
CAs
from
pathogenic
bacteria,
fungi,
protozoans,
nematodes
started
be
considered
recent
years,
with
notable
advances
registered.
CAIs
a
complex
multipharmacology
probably
unique
this
enzyme,
which
has
exploited
intensely
but
may
lead
other
relevant
future
due
emergence
design
approaches
that
afforded
highly
isoform-selective
compounds
most
α-CAs
date.
belong
multitude
chemical
classes
(sulfonamides
isosteres,
[iso]coumarins
related
compounds,
mono-
dithiocarbamates,
selenols,
ninhydrines,
boronic
acids,
benzoxaboroles,
etc).
polypharmacology
will
also
discussed
because
drugs
originally
discovered
treatment
non-CA
conditions
(topiramate,
zonisamide,
celecoxib,
pazopanib,
thiazide,
high-ceiling
diuretics)
show
effective
inhibition
against
many
CAs,
led
repurposing
diverse
applications.
SIGNIFICANCE
STATEMENT:
multiple
pharmacologic
applications,
such
antiobesity,
antiacute
anti-idiopathic
drugs.
Their
neurodegenerations
investigated
recently.
Parasite
anhydrases
anti-infectives
novel
mechanisms
action
can
bypass
resistance
commonly
Drugs
effectively
inhibit
these
enzymes
exert
interesting
polypharmacologic
effects.
Язык: Английский
Unveiling the antiurolithiatic potentiality of two benzene sulfonamide derivatives against ethylene glycol-induced renal calculi
Nefrología (English Edition),
Год журнала:
2025,
Номер
45(2), С. 167 - 181
Опубликована: Фев. 1, 2025
Oxidative
stress
and
inflammation
play
crucial
roles
in
the
onset
of
kidney
injury
crystal
formation
caused
by
hyperoxaluria.
Indapamide
is
a
potent
medication
for
treating
renal
calculi,
but
it
has
severe
side
effects
such
as
hypokalemia,
hypercalcemia,
hyperuricemia.
Therefore,
advisable
to
explore
alternative
treatments
that
do
not
have
these
effects.
The
study
aimed
reveal
antiurolithiatic
potential
two
benzene
sulfonamide
derivatives
(SBCl
SBF;
A
B,
respectively)
against
ethylene
glycol-induced
stones.
rats
were
divided
into
main
groups:
first
group
consisted
20
with
induced
stones,
second
included
15
control
rats.
This
division
enabled
comparative
analysis
between
stones
those
without,
offering
insights
stone
induction
on
various
physiological
parameters
biochemical
markers.
effectiveness
(compounds
B)
was
assessed
treatment
given
orally
gavage
21
days,
administered
every
48h
after
inducing
0.12ml
5%
glycol
(EG).
influence
compounds
B
electrolytes,
biochemical,
antioxidant,
inflammatory
reactions
kidneys
underscores
their
therapeutic
advantages
alleviating
advancement
disease
related
complications.
Both
found
possess
equal
inhibiting
complications
formation.
However,
SBCl-EG
showed
superior
antioxidant
compared
SBF-EG.
Our
study's
findings
underscore
benefits
nephrolithiasis
oxidative
disorders,
highlighting
responses
standard
treatments.
Язык: Английский
Effectiveness of Topiramate Versus Acetazolamide in the Management of Idiopathic Intracranial Hypertension: ASystematic Review and Meta-Analysis
Medicina,
Год журнала:
2025,
Номер
61(3), С. 450 - 450
Опубликована: Март 4, 2025
Background
and
Objectives:
Primary
pseudotumor
cerebri
syndrome,
another
name
for
idiopathic
intracranial
hypertension
(IIH),
is
a
neurological
condition
marked
by
elevated
pressure
(ICP)
that
can
result
in
papilledema
without
known
etiology.
The
purpose
of
this
study
to
compare
the
efficacy
topiramate
acetazolamide
as
medical
treatments
IIH
evaluate
long-term
outcomes
both
medications.
Materials
Methods:
This
systematic
review
meta-analysis
followed
PRISMA
guidelines
was
approved
International
Prospective
Register
Systematic
Reviews
(PROSPERO).
included
randomized
clinical
trials,
retrospective
prospective
cohort
studies,
patients
with
(IIH).
Data
extraction
performed
using
Rayyan
application,
risk
bias
assessed
Critical
Appraisal
Skills
Program
(CASP).
Results:
findings
revealed
statistically
significant
67%
increase
likelihood
improvement
at
6
months
compared
baseline
administration
topiramate.
After
six
drug
administration,
there
3.6
times
decrease
visual
obscuration
baseline.
A
advantage
added
benefit
weight
loss,
since
obesity
modifiable
factor.
However,
remains
conventional
treatment.
Conclusions:
found
are
effective
therapies
improving
metrics
decreasing
cerebrospinal
fluid
pressure.
Topiramate
aids
reduction,
while
recommended
its
ability
lower
CSF
alleviate
changes.
combination
treatment
better
results.
Язык: Английский
Development of novel amino-benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors: Design, synthesis, anticancer activity assessment, and pharmacokinetic studies using UPLC-MS/MS
Bioorganic Chemistry,
Год журнала:
2025,
Номер
159, С. 108335 - 108335
Опубликована: Март 6, 2025
Язык: Английский
Comprehensive Insights into Carbonic Anhydrase Inhibition: A Triad of In vitro, In silico, and In vivo Perspectives
Enzyme and Microbial Technology,
Год журнала:
2025,
Номер
189, С. 110657 - 110657
Опубликована: Апрель 17, 2025
Язык: Английский
Bacterial ι-CAs
The Enzymes,
Год журнала:
2024,
Номер
unknown, С. 121 - 142
Опубликована: Янв. 1, 2024
Язык: Английский
Characterization of human Aquaporin ion channels in a yeast expression system as a tool for novel ion channel discovery
Bioscience Reports,
Год журнала:
2024,
Номер
44(8)
Опубликована: Июль 29, 2024
Abstract
Aquaporin
(AQP)
channels
found
in
all
domains
of
life
are
transmembrane
proteins
which
mediate
passive
transport
water,
glycerol,
signaling
molecules,
metabolites,
and
charged
solutes.
Discovery
new
classes
ion-conducting
AQP
has
been
slow,
likely
reflecting
time-
labor-intensive
methods
required
for
traditional
electrophysiology.
Work
here
defines
a
sensitive
mass-throughput
system
detecting
ion
channels,
identified
by
rescue
cell
growth
the
K+-transport-defective
yeast
strain
CY162
following
genetic
complementation
with
heterologously
expressed
cation-permeable
using
well
characterized
human
AQP1
channel
proof
concept.
Results
showed
conferred
permeability
to
cations
rescued
survival
yeast.
Comprehensive
testing
that
response
properties
fully
recapitulated
pharmacological
agonist
antagonist
profiles
activation,
inhibition,
dose-dependence,
structure–function
relationships,
demonstrating
validity
screening
tool
identification
drug
discovery
efforts.
This
method
also
provided
information
on
divalent
cation
blockers
AQP1,
pH
sensitivity
antagonists,
AQP6.
Site-directed
mutagenesis
regulatory
confirmed
was
mediated
introduced
channels.
Optical
monitoring
lithium-sensitive
photoswitchable
probe
living
cells
independently
demonstrated
monovalent
plasma
membrane.
Ion
were
consistent
those
Xenopus
laevis
oocyte
K+-transport
defective
Escherichia
coli.
Outcomes
establish
powerful
approach
efficient
phylogenetically
diverse
AQPs
yet
untested
functions
as
Язык: Английский