Abstract
In
this
study,
new
benzoic
acid
derivatives
of
the
quinazolinone
ring,
which
is
one
biologically
active
members
nitrogen‐containing
heterocyclic
compounds,
were
synthesized
with
excellent
yields
(98–90
%).
The
structures
novel
compounds
(
1
–
12
)
characterized
Fourier‐transform
Infrared
(FTIR),
Nuclear
Magnetic
Resonance
H
NMR–
13
C
NMR),
and
High‐Resolution
Mass
Spectroscopy
(HRMS).
α‐Glucosidase
α‐Amylase
inhibition
properties
examined
to
evaluate
anti‐diabetic
compounds.
For
α‐Glucosidase,
molecules
showed
IC
50
in
ranging
>100–3.468±0.270
μM
K
i
s
>100–3.310±0.326
μM.
α‐Amylase,
>100–1.215±0.225
4‐[(2‐[(4‐phenylpiperazin‐1‐yl)methyl]‐4‐oxoquinazolin‐3(4
)‐ylimino)methyl]benzoicacid
10
has
strongest
inhibitory
effect
for
both
enzymes.
It
5.4
times
more
potent
inhibitor
34.9
than
standard
Acarbose.
Also,
molecular
docking
study
was
carried
out
most
compound
determination
ligand‐enzyme
interactions.
Binding
affinities
calculated
as
−5.978
kcal/mol
−5.548
respectively.
aromatic
ring
aminomethyl
group
quinazoline
carboxyl
moieties
have
played
a
critical
role
inhibition.
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.
Frontiers in Chemistry,
Год журнала:
2024,
Номер
12
Опубликована: Авг. 7, 2024
The
spread
of
drug-resistant
tuberculosis
strains
has
become
a
significant
economic
burden
globally.
To
tackle
this
challenge,
there
is
need
to
develop
new
drugs
that
target
specific
mycobacterial
enzymes.
Among
these
enzymes,
InhA,
which
crucial
for
the
survival
Mycobacterium
,
key
drug
development.
Herein,
24
compounds
were
synthesized
by
merging
4-carboxyquinoline
with
triazole
motifs.
These
molecules
then
tested
their
effectiveness
against
different
tuberculosis,
including
M.
bovis
BCG
and
abscessus
.
Additionally,
ability
inhibit
InhA
enzyme
was
also
evaluated.
Several
showed
potential
as
inhibitors
Compound
5n
displayed
highest
efficacy
MIC
value
12.5
μg/mL.
Compounds
5g
5i
exhibited
inhibitory
effects
on
InhA.
Notably,
activity
compared
reference
Isoniazid.
Molecular
docking
analysis
revealed
interactions
between
enzyme.
molecular
dynamic
simulations
confirmed
stability
complexes
formed
quinoline-triazole
conjugate
Finally,
underwent
in
silico
predict
its
ADME
characteristics.
findings
provide
promising
insights
developing
novel
small
are
safe
effective
global
fight
tuberculosis.
Future Medicinal Chemistry,
Год журнала:
2023,
Номер
15(14), С. 1233 - 1250
Опубликована: Июль 1, 2023
Background:
VEGFR-2
is
one
of
the
most
effective
targets
in
cancer
treatment.
Aim:
The
design
and
semi-synthesis
new
theobromine
derivatives
as
potential
inhibitors.
Methods:
In
vitro
silico
evaluation
synthesized
compounds.
Results:
Compound
5b
demonstrated
excellent
antiproliferative
inhibitory
effects
with
significant
apoptotic
activity.
It
modulated
immune
response
by
increasing
IL-2
reducing
TNF-α
levels.
Docking
molecular
dynamics
simulations
revealed
compound’s
binding
affinity
VEGFR-2.
Lastly,
computational
absorption,
distribution,
metabolism,
excretion
toxicity
studies
indicated
high
compound
for
drug
development.
Conclusion:
could
be
a
promising
anticancer
agent
targeting
