Al Mustansiriyah Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
24(2), С. 137 - 149
Опубликована: Апрель 8, 2024
New
benzene
sulfonamide
compounds
4–10
was
modeled
at
the
molecular
level
to
reveal
binding
opportunities,
bond
length,
angle,
and
energy
scores
in
CA
II,
CAXII,
CAIX
active
sites.
To
test
their
cytotoxic
effect
against
AMJ-13
Iraqi
breast
cancer
cell
line,
researchers
synthesized
promising
from
4-(2-mercapto-4-oxoquinazolin-3(4H)-yl)
3.
Derivatives
have
IC50
values
between
0.10
6.47
M,
indicating
potent
action
line.
The
most
effective
of
these
were
numbers
4,
7,
10.
highest
site
CAXII
seen
for
drugs,
which
may
explain
inhibitory
profile.
Expert Opinion on Therapeutic Patents,
Год журнала:
2023,
Номер
33(11), С. 701 - 720
Опубликована: Авг. 7, 2023
ABSTRACTIntroduction
Several
isoforms
of
the
metalloenzyme
carbonic
anhydrase
(CA,
EC
4.2.1.1)
are
connected
with
tumorigenesis.
Hypoxic
tumors
overexpress
CA
IX
and
XII
as
a
consequence
HIF
activation
cascade,
being
involved
in
pH
regulation,
metabolism,
metastases
formation.
Other
(CA
I,
II,
III,
IV)
were
also
reported
to
be
present
some
tumors.Areas
Covered
Some
biomarkers
for
disease
progression
or
response
therapy.
Inhibitors,
antibodies,
other
procedures
targeting
these
enzymes
treatment
tumors/metastases
discussed.
Sulfonamides
coumarins
represent
most
investigated
classes
inhibitors,
but
carboxylates,
selenium,
tellurium-containing
inhibitors
investigated.
Hybrid
drugs
antitumor
agents
multitargeted
therapy
reported.Expert
opinion
Targeting
CAs
solid
hematological
selective,
targeted
is
validated
approach,
which
has
been
consolidated
last
years.
A
host
new
preclinical
data
several
clinical
trials
antibodies
small-molecule
ongoing,
large
number
chemotypes/procedures
discovered
effective,
may
lead
breakthrough
this
therapeutic
area.
The
scientific/patent
literature
searched
on
PubMed,
ScienceDirect,
Espacenet,
PatentGuru,
from
2018
2023.KEYWORDS:
anhydraseanticancer
drugshypoxic
tumorinhibitorssulfonamidescoumarinsantibodieshybrid
Article
highlights
hCA
expressed
hypoxic
tumor
cells,
promoting
growth
metastasis
formation
tumorsIsoforms
such
IV
found
many
types,
considered
novel
targetsExosomes
patients
enriched
cancer-associated
CAs,
IXA
available,
chemotypes
periodSulfonamides
prevalently
isoform-selective
compounds
available
dateNovel
chemotypes,
incorporating
selenium
tellurium
obtained,
contribute
effects
by
additional
mechanisms
actionHybrid
(estrogen
receptor
modulators;
vascular
endothelial
factor
2
antagonists;
H2S
releasing
agents;
signal
transducer
transcriptional
activator
3
mono-
triterpenes)
possess
enhanced
antitumor/antimetastatic
effectsSeveral
MAbs
one
sulfonamide
inhibitor
(SLC-0111)
under
evaluation
various
phases
development.Declaration
interestsClaudiu
T
Supuran
declares
conflict
interest
discoverer
SLC-0111
phase
Ib/II
trials.
author
no
relevant
affiliations
financial
involvement
any
organization
entity
subject
matter
materials
discussed
manuscript
apart
those
disclosed.Reviewer
disclosuresPeer
reviewers
have
relationships
disclose.Additional
informationFundingThis
paper
was
not
funded.
This
study
introduces
a
series
of
ten
hybrid
molecules
DK(1-10),
which
combine
diazo
and
coumarin
moieties
along
with
diverse
aromatic
substitutions.
The
primary
objective
was
to
evaluate
the
inhibitory
capabilities
these
compounds
against
four
prominent
isoforms:
cytosolic
hCA
I
II,
as
well
tumor-associated
membrane-bound
IX
XII.
Impressively,
majority
tested
exhibited
significant
inhibition
activity
isoforms
XII,
K
Abstract
In
this
study,
we
present
the
re‐synthesis
of
a
series
twelve
bis‐ureido‐substituted
benzenesulfonamides,
focusing
on
their
potential
as
antibacterial,
anticholinesterase,
and
cytotoxic
agents.
First,
antibacterial
assessment
these
compounds
indicated
varying
activity
levels
across
different
bacterial
strains,
with
S.
aureus
displaying
resistance
to
all
compounds,
while
9
11
exhibited
promise
against
E.
faecalis
MIC
value
31.25
μg/mL.
Additionally,
P.
aeruginosa
showed
containing
4‐aminobenzene
sulfonamides,
whereas
derivatives
such
(
8
–
)
compound
19
displayed
notable
coli
,
comparable
Ampicillin.
Second,
anticholinesterase
activities
were
examined,
focus
role
in
addressing
neurological
disorders,
particularly
Alzheimer′s
disease.
The
findings
that
synthesized
significant
inhibitory
effect
both
AChE
BChE
enzymes.
Compound
demonstrated
most
effective
inhibition
enzyme
an
IC
50
0.2160±0.09
nM,
18
potent
0.2257±0.06
nM.
Finally,
cytotoxicity
studies
conducted
various
cell
lines,
including
breast,
lung,
prostate
cancer
cells
normal
cells.
results
revealed
12
emerged
tested
breast
no
CRL‐4010
epithelial
research
presented
here
not
only
highlights
multifaceted
pharmacological
but
also
indicates
versatile
for
applications,
opening
up
new
avenues
drug
discovery
development.
Archiv der Pharmazie,
Год журнала:
2024,
Номер
357(8)
Опубликована: Май 7, 2024
Abstract
Two
novel
series
of
hydrazinyl‐based
benzenesulfonamides
9a
–
j
and
10a
were
designed
synthesized
using
SLC‐0111
as
the
lead
molecule.
The
newly
compounds
evaluated
for
their
inhibitory
activity
against
four
different
human
carbonic
anhydrase
(hCA)
isoforms
I,
II,
IX,
XII.
Both
reported
here
practically
inactive
off‐target
isozyme
hCA
I.
Notably,
derivative
exhibited
superior
potency
(
K
i
10.2
nM)
than
acetazolamide
(AAZ)
cytosolic
isoform
II.
IX
XII
implicated
in
tumor
progression
effectively
inhibited
with
s
low
nanomolar
range
20.5–176.6
nM
6.0–127.5
nM,
respectively.
Compound
9g
emerged
most
potent
selective
inhibitor
20.5
S
I
200.1,
6.0
683.7,
respectively,
over
Furthermore,
six
,
9h
10g
10i
10j
)
significant
inhibition
toward
=
27.0,
41.1,
27.4,
25.9,
40.7,
30.8
relative
to
AAZ
25.0
45.0
respectively).
These
findings
underscore
potential
these
derivatives
inhibitors
Anti-Cancer Agents in Medicinal Chemistry,
Год журнала:
2024,
Номер
24(10), С. 755 - 763
Опубликована: Фев. 16, 2024
The
aim
of
this
study
was
to
synthesize
a
library
novel
di-sulfa
drugs
containing
1,3-
diaryltriazene
derivatives
TS
(1-13)
by
conjugation
diazonium
salts
primary
sulfonamides
with
sulfa
investigate
the
cytotoxic
effect
these
new
compounds
in
different
cancer
types
and
determine
their
inhibitory
activity
against
tumor-associated
carbonic
anhydrases
IX
XII.
