Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2020,
Номер
35(1), С. 1011 - 1020
Опубликована: Янв. 1, 2020
The
clinically
used
antibiotic
Furagin
and
its
derivatives
possess
inhibitory
activity
on
human
(h)
carbonic
anhydrases
(CA,
EC
4.2.1.1),
some
of
which
are
highly
expressed
in
various
tissues
malignancies
(hCA
IX/XII).
exhibited
good
hCA
IX
XII
inhibition
with
KIs
260
57
nM,
respectively.
It
does
not
inhibit
off-target
CA
I
poorly
inhibited
II
(KI
=
9.6
μM).
Some
synthesised
aminohydantoin
moieties
as
zinc
binding
group
weak
I/II,
IX/XII
ranging
from
350
to
7400
150
5600
Docking
molecular
dynamics
simulations
suggest
that
selectivity
for
the
cancer-associated
over
is
due
strong
H-bond
interactions
IX/XII,
involving
tail
orientated
towards
hydrophobic
area
active
site.
These
results
a
possible
drug
repurposing
anti-cancer
agent.
Pharmaceuticals,
Год журнала:
2022,
Номер
15(5), С. 536 - 536
Опубликована: Апрель 27, 2022
Isatin,
chemically
an
indole-1H-2,3-dione,
is
recognised
as
one
of
the
most
attractive
therapeutic
fragments
in
drug
design
and
development.
The
template
has
turned
out
to
be
exceptionally
useful
for
developing
new
anticancer
scaffolds,
evidenced
by
increasing
number
isatin-based
molecules
which
are
either
clinical
use
or
trials.
Apart
from
its
promising
antiproliferative
properties,
isatin
shown
potential
treating
Neglected
Tropical
Diseases
(NTDs)
not
only
a
parent
core,
but
also
attenuating
activities
various
pharmacophores.
objective
this
mini-review
keep
readers
up
date
on
latest
developments
biological
targeting
cancer
NTDs
such
tuberculosis,
malaria,
microbial
infections.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2023,
Номер
38(1)
Опубликована: Апрель 25, 2023
In
this
work,
new
isatin-based
sulphonamides
(6a-i,
11a-c,
12a-c)
were
designed
and
synthesised
as
potential
dual
VEGFR-2
carbonic
anhydrase
inhibitors
with
anticancer
activities.
Firstly,
all
target
isatins
examined
for
in
vitro
antitumor
action
on
NCI-USA
panel
(58
tumour
cell
lines).
Then,
the
most
potent
derivatives
CA
inhibitory
towards
physiologically
relevant
hCA
isoforms
I,
II,
tumour-linked
IX
isoform,
addition,
activity
was
evaluated.
The
failed
to
inhibit
that
could
be
attributable
steric
effect
of
neighbouring
methoxy
group,
whereas
they
displayed
effect.
Following
that,
11b
12b
tested
their
influence
cycle
disturbance,
apoptotic
potential.
Finally,
detailed
molecular
modelling
analyses,
including
docking
dynamics,
carried
out
assess
binding
mode
stability
isatins.
ACS Omega,
Год журнала:
2023,
Номер
8(20), С. 17446 - 17498
Опубликована: Май 9, 2023
Innate
inflammation
beyond
a
threshold
is
significant
problem
involved
in
cardiovascular
diseases,
cancer,
and
many
other
chronic
conditions.
Cyclooxygenase
(COX)
enzymes
are
key
inflammatory
markers
as
they
catalyze
prostaglandins
production
crucial
for
processes.
While
COX-I
constitutively
expressed
generally
"housekeeping"
roles,
the
expression
of
COX-II
isoform
induced
by
stimulation
different
cytokines
also
promotes
further
generation
pro-inflammatory
chemokines,
which
affect
prognosis
various
diseases.
Hence,
considered
an
important
therapeutic
target
drug
development
against
inflammation-related
illnesses.
Several
selective
inhibitors
with
safe
gastric
safety
profiles
features
that
do
not
cause
gastrointestinal
complications
associated
classic
anti-inflammatory
drugs
have
been
developed.
Nevertheless,
there
mounting
evidence
side
effects
from
resulted
withdrawal
market-approved
anti-COX-II
drugs.
This
necessitates
only
exhibit
inhibit
potency
but
free
effects.
Probing
scaffold
diversity
known
vital
to
achieving
this
goal.
A
systematic
review
discussion
on
COX
still
limited.
To
address
gap,
herein
we
present
overview
chemical
structures
inhibitory
activity
scaffolds
inhibitors.
The
insights
article
could
be
helpful
seeding
next-generation
Molecular Diversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 4, 2024
Abstract
The
emergence
of
diverse
infections
worldwide,
which
is
a
serious
global
threat
to
human
existence,
necessitates
the
urgent
development
novel
therapeutic
candidates
that
can
combat
these
diseases
with
efficacy.
Molecular
hybridization
has
been
established
as
an
efficient
technique
in
designing
bioactive
molecules
capable
fighting
infections.
Isatin,
core
nucleus
array
compounds
biological
properties
be
modified
at
different
positions
leading
creation
drug
targets,
active
area
medicinal
chemistry.
This
review
containing
published
articles
from
2005
2022
highlights
isatin
hybrids
have
synthesized
and
reported
literature
alongside
discussion
on
their
properties.
enriched
structure–activity
relationship
studies
discussed
provides
insights
for
rational
design
tailored
effective
inspired
by
nature.
