Recent Patents on Anti-Cancer Drug Discovery,
Journal Year:
2021,
Volume and Issue:
17(3), P. 284 - 296
Published: Dec. 23, 2021
Background:
Finding
novel
antitumor
reagents
from
naturally
occurring
alkaloids
is
a
widely
accepted
strategy.
Evodiamine,
tryptamine
indole
alkaloid
isolated
Evodia
rutaecarpa,
has
wide
range
of
biological
activities,
such
as
anti-tumor,
anti-inflammation,
and
anti-bacteria.
Hence,
research
on
the
structural
modification
evodiamine
will
facilitate
discovery
new
drugs.
Objective:
The
recent
advances
in
synthesis
evodiamine,
studies
drug
design,
structure-activity-relationships
its
derivatives,
published
patents
primary
literature,
are
reviewed
this
paper.
Methods:
including
follow-up
papers
2015
to
2020,
related
searched
Scifinder,
PubMed,
Espacenet,
China
National
Knowledge
Infrastructure
(CNKI),
Wanfang
databases.
keywords
synthesis,
modification,
anticancer,
mechanism.
Results:
summarized.
Then,
modifications
described,
possible
modes
action
discussed.
Conclusion:
Evodiamine
6/5/6/6/6
ring
system,
focused
rings
A,
D,
E,
C5,
N-13,
N-14.
Some
compounds
show
promising
anticancer
potentials
warrant
further
study.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2020,
Volume and Issue:
39(1)
Published: Nov. 19, 2020
Abstract
Background
Accumulating
evidence
showed
that
regulating
tumor
microenvironment
plays
a
vital
role
in
improving
antitumor
efficiency.
Programmed
Death
Ligand
1
(PD-L1)
is
expressed
many
cancer
cell
types,
while
its
binding
partner
(PD1)
activated
T
cells
and
antigen-presenting
cells.
Whereas,
dysregulation
the
poorly
understood.
In
present
study,
we
confirmed
evodiamine
downregulates
MUC1-C,
resulting
modulating
PD-L1
expression
non-small
lung
(NSCLC).
Methods
Cell
viability
was
measured
by
MTT
assays.
Apoptosis,
cycle
surface
on
NSCLC
were
analyzed
flow
cytometry.
The
of
MUC1-C
mRNA
real
time
RT-PCR
methods.
Protein
examined
evodiamine-treated
using
immunoblotting
or
immunofluorescence
effects
treatment
sensitivity
towards
investigated
human
peripheral
blood
mononuclear
Jurkat,
apoptosis
IL-2
secretion
Female
H1975
xenograft
nude
mice
used
to
assess
effect
tumorigenesis
vivo.
Lewis
carcinoma
model
investigate
therapeutic
combination
anti-PD-1
treatment.
Results
We
significantly
inhibited
growth,
induced
arrest
at
G2
phase
Evodiamine
suppressed
IFN-γ-induced
H1650.
protein
decreased
as
well.
could
downregulate
diminish
It
potentiated
CD8
+
effector
function.
Meanwhile,
good
anti-tumor
activity
,
which
reduced
size.
exhibited
elevation
vivo
model.
Combination
mAb
enhanced
growth
control
survival
mice.
Conclusions
can
suppress
elevating
downregulating
MUC1-C/PD-L1
axis.
Our
findings
uncover
novel
mechanism
action
indicate
represents
potential
targeted
agent
suitable
be
combined
with
immunotherapeutic
approaches
treat
patients.
overexpression
common
female,
non-smoker,
patients
advanced-stage
adenocarcinoma.
Organic Letters,
Journal Year:
2021,
Volume and Issue:
23(3), P. 863 - 868
Published: Jan. 19, 2021
Epoxides
as
alkylating
reagents
are
unprecedentedly
applied
in
Pd(II)-catalyzed
C–H
alkylation
and
oxidative
annulation
of
substituted
benzamides
to
synthesize
isoquinolones
rather
than
isochromans,
which
is
accomplished
through
alerting
the
previously
reported
reaction
mechanism
by
addition
oxidant
TEA.
Under
these
conditions,
various
have
been
prepared
with
yields
up
92%.
In
addition,
this
methodology
has
successfully
employed
total
syntheses
rupreschstyril,
siamine,
cassiarin
A
an
expedient
fashion.
Journal of Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
64(23), P. 17346 - 17365
Published: Nov. 30, 2021
Evodiamine
(Evo)
is
a
quinazolinocarboline
alkaloid
found
in
Evodia
rutaecarpa
and
exhibits
moderate
antiproliferative
activity.
Herein,
we
report
using
scaffold-hopping
approach
to
identify
series
of
novel
polycyclic
heterocyclic
derivatives
based
on
Evo
as
the
topoisomerase
I
(Top1)
inhibitor
for
treatment
triple-negative
breast
cancer
(TNBC),
which
an
aggressive
subtype
with
limited
options.
The
most
potent
compound
7f
inhibited
cell
growth
human
carcinoma
line
(MDA-MB-231)
IC50
value
0.36
μM.
Further
studies
revealed
that
Top1
was
target
7f,
directly
induced
irreversible
Top1–DNA
covalent
complex
formation
or
oxidative
DNA
lesion
through
indirect
mechanism
mediated
by
reactive
oxygen
species.
More
importantly,
vivo
showed
exhibited
antitumor
activity
TNBC-patient-derived
tumor
xenograft
model.
These
results
suggest
deserves
further
investigation
promising
candidate
TNBC.
Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(11), P. 7975 - 7992
Published: May 31, 2022
Evodiamine
has
many
biological
activities.
Herein,
we
synthesize
23
disubstituted
derivatives
of
N14-phenyl
or
the
E-ring
evodiamine
and
conduct
systematic
structure–activity
relationship
studies.
In
vitro
antiproliferative
activity
indicated
that
compounds
F-3
F-4
dramatically
inhibited
proliferation
Huh7
(IC50
=
0.05
0.04
μM,
respectively)
SK-Hep-1
0.07
0.06
cells.
Furthermore,
could
double
inhibit
topoisomerases
I
II,
invasion
migration,
block
cell
cycle
to
G2/M
stage,
induce
apoptosis
as
well.
Additionally,
also
activation
HSC-T6
reduce
secretion
collagen
type
slow
down
progression
liver
fibrosis.
Most
importantly,
compound
(TGI
60.36%)
tumor
growth
more
significantly
than
positive
drug
sorafenib.
To
sum
up,
excellent
potential
a
strong
candidate
for
therapy
hepatocellular
carcinoma.
