Molbank,
Journal Year:
2024,
Volume and Issue:
2024(4), P. M1920 - M1920
Published: Nov. 19, 2024
The
title
compound,
trans-11-(3,4-Dimethoxyphenyl)-2,3,8,9-tetramethoxy-6-oxo-11,12-dihydro-6H-dibenzo[c,h]chromene-12-carboxylic
acid
(4),
was
synthesized
for
the
first
time
via
a
two-step
protocol
from
3,4-dimethoxyhomophthalic
anhydride
(1)
and
3,4-dimethoxybenzaldehyde
(DMBA).
In
step,
1
reacts
with
DMBA
to
give
trans-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1-oxo-3,4-dihydro-1H-2-benzopyran-4-carboxylic
(2),
which
further
two
additional
equivalents
of
4.
Compound
4
characterized
by
means
spectral
methods—1H-,
13C-,
DEPT-135-NMR,
HRMS.
European Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
276, P. 116697 - 116697
Published: July 18, 2024
Copper
complexes
have
shown
promising
anticancer
properties,
but
they
are
often
poorly
soluble
in
aqueous
solutions,
thus
limiting
their
possible
medical
developments
and
applications.
We
recently
isolated
some
copper(II)
with
salicylaldehyde
thiosemicarbazone
ligands
exhibiting
remarkable
nanomolar
cytotoxic
activity,
vivo
tests
evidenced
several
difficulties
related
to
poor
solubility.
To
overcome
these
limitations
increase
solubility
solution,
herein
we
report
the
synthetic
strategy
that
led
introduction
of
sulfonic
group
on
ligands,
then
separated
as
salts
(NaH
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 15, 2025
Among
the
smaller
substituents
in
medicinal
chemist's
toolbox,
hydroxy
(OH)
group
can
bestow
one
of
largest
impacts
drug-like
properties
a
molecule.
A
previous
study
showed
that
an
H-to-OH
structural
modification
effectively
decreases
lipophilicity,
increases
solubility,
and
hERG
inhibition.
Despite
these
benefits,
OH
is
not
always
recommended
drug
molecules
because
it
presents
metabolic
"soft
spot"
for
oxidation
glucuronidation
primary
secondary
alcohols.
Furthermore,
challenges
permeability.
In
contrast,
tertiary
alcohols
(3°
ROH)
often
display
improved
profile
at
3°
ROH
possible,
geminal
alkyl
groups
could
sterically
shield
from
permeability
challenges.
Through
series
matched
molecular
pairs,
this
Perspective
highlights
as
motif
reap
benefits
but
minimize
drawbacks
discovery.
Chemistry & Biodiversity,
Journal Year:
2024,
Volume and Issue:
21(12)
Published: Aug. 19, 2024
Abstract
In
this
study,
some
new
hydrazone
derivatives
(
2a
–
g
)
was
designed,
synthesized
for
first
time,
and
evaluated
as
multitarget
inhibitors
of
AChE,
BChE,
hCA
I
II.
The
chemical
structures
hybrids
were
confirmed
by
elemental
analysis
spectroscopic
techniques.
All
tested
compounds
showed
low
nanomolar
inhibition
with
IC
50
values
in
the
range
30.4–264.0
nM
against
I,
23.2–251.6
II,
12.1–114.3
76.4–134.0
BChE.
These
inhibited
AChE
more
than
acetazolamide
(AZA)
neostigmine.
Among
them,
2c
2e
,
which
have
a
linear
structure,
determined
to
be
most
active
inhibitor
candidates
these
selected
enzymes.
Molecular
docking
studies
carried
out
on
2a‐
‐
),
revealing
their
binding
interactions
site
II
thus
supporting
experimental
findings.
Additionally,
silico
absorption,
distribution,
metabolism,
excretion
(ADME)
prediction
obtained
approaches
determine
solubility,
whether
they
potential
cross
blood‐brain
barrier
(BBB),
such
GI
absorption
drug
likeness
principles.
Molecules,
Journal Year:
2025,
Volume and Issue:
30(2), P. 346 - 346
Published: Jan. 16, 2025
2-phenylchromen-4-one,
commonly
known
as
flavone,
plays
multifaceted
roles
in
biological
response
that
can
be
abundantly
present
natural
sources.
The
methoxy
group
naturally
occurring
flavones
promotes
cytotoxic
activity
various
cancer
cell
lines
by
targeting
protein
markers,
facilitating
ligand-protein
binding
mechanisms
and
activating
cascading
downstream
signaling
pathways
leading
to
death.
However,
the
lipophilic
nature
of
these
analogs
is
a
key
concern
it
impacts
drug
membrane
transfer.
While
lipophilicity
crucial
for
efficacy,
excessive
effects
flavonoids
reduce
water
solubility
hinder
transport
target
sites.
Recent
vitro
studies
suggest
incorporation
polar
hydroxyl
groups
which
form
hydrogen
bonds
stabilize
free
radicals
may
help
overcome
challenges
associated
with
while
maintaining
their
essential
properties.
Naturally
coexisting
methoxyflavones,
this
review
explores
synergistic
role
hydroxy
moieties
through
bonding
capacity
maximizing
cytotoxicity
against
lines.
physicochemical
analysis
revealed
potential
intramolecular
interaction
favorable
electron
delocalization
region
between
both
improve
levels.
Together,
provides
useful
strategy
structure-activity
relationship
(SAR)
flavonoid
distinct
suggesting
optimal
functional
positioning
achieve
balanced
lipophilicity,
effective
bonding,
simultaneously
minimized
steric
hindrance
specific
types.
RSC Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
PIM-1
is
a
type
of
serine/threonine
kinase
that
plays
crucial
role
in
controlling
several
vital
processes,
including
proliferation
and
apoptosis.
New
synthetic
S-amide
tetrahydropyrimidinone
derivatives
were
designed
synthesized
as
inhibitors
with
potential
anticancer
activity.
Several
biochemical
assays
performed
for
assessment,
inhibitory
assays,
MTT,
apoptosis
cell
cycle,
gene
expression
analysis,
c-MYC
ATPase
assays.
Compounds
(8c,
8d,
8g,
8h,
8k,
8l)
exhibited
strong
vitro
broad
antiproliferative
activity
against
MCF-7,
DU-145,
PC-3,
relatively
higher
SI
index
suggesting
minimal
cytotoxicity
to
normal
cells.
Furthermore,
these
compounds
induced
mixed
late
necrosis
cycle
arrest
at
the
G2/M
phase.
Moreover,
8b,
8f,
8l
showed
potent
action
kinase,
corresponding
IC50
values
660,
909,
373,
518,
501
nM.
In
silico
prediction
studies
physiochemical
properties,
molecular
dynamics,
fit
docking
explain
their
biological
conclusion,
new
pyrimidinone
exhibit
can
be
used
promising
scaffolds
further
optimization
leads
selective
PIM-inhibitors
