A
reliable
method
for
the
synthesis
of
bis-spirocyclic
derivatives
3-azabicyclo[3.1.0]hexane
through
1,3-dipolar
cycloaddition
(1,3-DC)
reactions
cyclopropenes
to
stable
azomethine
ylide
–
protonated
form
Ruhemann's
Purple
(PRP)
has
been
developed.
Both
3-substituted
and
3,3-disubstituted
reacted
with
PRP,
affording
corresponding
cycloadducts
in
moderate
good
yields
high
diastereofacial
selectivity.
Moreover,
several
unstable
1,2-disubstituted
were
successfully
trapped
by
1,3-dipole
under
mild
conditions.
The
mechanism
PRP
thoroughly
studied
using
density
functional
theory
(DFT)
methods
at
M11/cc-pVDZ
level
theory.
have
found
be
HOMO
cyclopropene
LUMO
controlled
while
transition-state
energies
reaction
3-methyl-3-phenylcyclopropene
are
fully
consistent
experimentally
observed
stereoselectivity.
The Journal of Organic Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 27, 2025
An
efficient
one-pot
three-component
[3
+
2]-cycloaddition
reaction
of
azomethine
ylides,
generated
in
situ
from
isatins
and
azetidine-2-carboxylic
acid,
with
different
maleimides
itaconimides
has
been
investigated.
These
reactions
afford
the
corresponding
spiro
dispiro[1-azabicyclo[3.2.0]heptanes]
moderate
to
high
yields
(up
93%)
excellent
diastereoselectivities
regioselectivities
under
mild
conditions.
The
method
provides
a
simple
route
stereoselective
synthesis
new
polyheterocyclic
systems
such
as
3-spiro[1-azabicyclo[3.2.0]heptane]oxindoles
spiro-conjugated
or
fused
succinimide
moiety.
observed
diastereo-
regioselectivity
cycloaddition
is
reasoned
by
DFT
studies.
antiproliferative
effect
synthesized
compounds
against
cancer
cell
lines
was
assessed.
Journal of Anatomy and Histopathology,
Journal Year:
2025,
Volume and Issue:
14(1), P. 74 - 82
Published: April 7, 2025
The
aim
was
to
conduct
a
comparative
pathomorphological
analysis
of
the
toxic
effects
new
spirofused
heterocyclic
compounds
on
rat
hippocampus.
Material
and
methods
.
Male
Wistar
rats
were
divided
into
3
groups.
Animals
control
group
injected
with
1
ml
saline
solution,
1st
experimental
(EG1)
given
single
intraperitoneal
injection
barbiturate,
animals
2nd
(EG2)
administered
oxindole
at
dose
12
mg/kg
animal’s
body
weight,
also
in
volume
ml.
2
8
weeks
after
administration
drugs,
taken
out
experiment.
Using
standard
histological
techniques,
5
μm
thick
sections
stained
toluidine
blue
using
Nissl
method.
Immunocytochemical
detection
astrocytic
glia
performed
antibodies
GFAP
protein.
Results
In
both
groups,
pyramidal
neurons
undergo
morphological
changes
typical
for
dying
cells.
Moreover,
from
EG2,
compared
group,
degenerative
detected
larger
number
all
fields
hippocampus,
while
EG1,
CA1
CA3
predominantly
affected.
Comparison
between
EG1
EG2
showed
that
has
greater
effect
CA4
fields.
It
established
morphometric
parameters
normalized
by
8th
week
experiment,
they
never
returned
values.
found
that,
despite
obvious
death
neurons,
proliferation
activation
astroglia
layer
does
not
occur.
contrast,
astrocytes
significantly
decreased
groups
group.
experiment
differed
those
EG1.
Conclusion
Spirofused
barbiturate
penetrate
blood-brain
barrier,
cause
areas
hippocampus
without
astrogliosis.
Among
two
studied
more
pronounced
glia.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(8), P. 3474 - 3474
Published: April 8, 2025
A
series
of
3-azabicyclo[3.1.0]hexanes
and
cyclopropa[a]pyrrolizidines
spiro-fused
to
acenaphthylene-1(2H)-one
aceanthrylene-1(2H)-one
frameworks
have
been
studied
for
their
in
vitro
antiproliferative
activity
against
human
erythroleukemia
(K562),
cervical
carcinoma
(HeLa),
melanoma
(Sk-mel-2),
osteosarcoma
(U2OS),
as
well
murine
(B16)
cell
lines.
Using
confocal
microscopy,
it
was
found
that
cultivation
with
the
tested
compounds
led
disappearance
stress
fibers
(granular
actin
distributed
diffusely
cytoplasm
up
56%
treated
cells)
decrease
filopodia-like
deformations
(up
69%
after
cultivation),
which
indirectly
suggests
a
motility.
The
line
scratch
test
showed
these
cells
lose
ability
move
do
not
fill
scratched
strip.
This
also
supported
by
docking
simulations
actin-related
targets
(PDB
ID:
8DNH,
2Q1N).
flow
cytometry,
impact
on
mitochondrial
membrane
potential
significant
increase
number
decreased
from
10%
control
55-80%
cyclopropa[a]pyrrolizidine
adducts.
obtained
results
support
antitumor
effect
spiro-compounds
encourage
extension
study
order
improve
anticancer
reduce
toxicological
risks.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(18), P. 10759 - 10759
Published: Sept. 15, 2022
A
series
of
heterocyclic
compounds
containing
spirofused
barbiturate
and
3-azabicyclo[3.1.0]hexane
frameworks
have
been
studied
as
potential
antitumor
agents.
Antiproliferative
activity
products
was
screened
in
human
erythroleukemia
(K562),
T
lymphocyte
(Jurkat),
cervical
carcinoma
(HeLa)
well
mouse
colon
(CT26)
African
green
monkey
kidney
epithelial
(Vero)
cell
lines.
The
most
effective
among
the
show
IC50
range
from
4.2
to
24.1
μM
for
all
tested
demonstrated
a
significant
effect
distribution
HeLa
CT26
cells
across
cycle
stage,
with
accumulation
SubG1
phase
induced
apoptosis.
It
found,
using
confocal
microscopy,
that
actin
filaments
disappeared
granular
distributed
diffusely
cytoplasm
up
90%
64%
after
treatment
3-azaspiro[bicyclo
[3.1.0]hexane-2,5′-pyrimidines].
We
discovered
number
filopodium-like
membrane
protrusions
reduced
significantly
(from
91%
control
35%)
active
compounds.
decrease
motility
also
noticed.
Preliminary
vivo
experiments
on
impact
dynamics
tumor
growth
Balb/C
mice
were
performed.
Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(12), P. 1582 - 1582
Published: Nov. 25, 2024
Background:
A
series
of
spiro-fused
heterocyclic
compounds
containing
cyclopropa[a]pyrrolizidine-2,3′-oxindole
and
3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole
frameworks
were
synthesized
studied
for
their
in
vitro
antiproliferative
activity
against
human
erythroleukemia
(K562),
cervical
carcinoma
(HeLa),
acute
T
cell
leukemia
(Jurkat),
melanoma
(Sk-mel-2)
breast
cancer
(MCF-7)
as
well
mouse
colon
(CT26)
lines.
Methods:
Cell
proliferation
was
evaluated
by
MTS
assay.
Confocal
microscopy
used
to
study
actin
cytoskeleton
structure
motility.
cycle
analysis
flow
cytometry.
Results:
It
found
that
4,
8,
18
24
showed
the
Jurkat,
K-562,
HeLa
Sk-mel-2
lines
with
IC50
ranging
from
2
10
μM
(72
h).
Evaluation
impact
on
progression
tested
achieved
significant
cell-cycle
perturbation
a
higher
accumulation
cells
SubG1
G0/G1
phases
cycle,
comparison
negative
control.
I
Incubation
led
disappearance
stress
fibers
(granular
distributed
diffusely
cytoplasm
up
38%
treated
cells)
changes
number
filopodia-like
deformations
(reduced
93%
control
64%
after
treatment).
The
even
greater:
granular
90%
while
reduced
23%.
scratch
test
performed
line
these
did
not
fill
scratched
strip
lose
ability
move
under
treatment.
Conclusions:
obtained
results
support
antitumor
effect
spiro-compounds
encourage
extension
this
order
improve
anticancer
reduce
toxicological
risks.
Beilstein Journal of Organic Chemistry,
Journal Year:
2022,
Volume and Issue:
18, P. 769 - 780
Published: June 29, 2022
A
reliable
method
for
the
synthesis
of
bis-spirocyclic
derivatives
3-azabicyclo[3.1.0]hexanes
through
1,3-dipolar
cycloaddition
(1,3-DC)
reactions
cyclopropenes
to
stable
azomethine
ylide
-
protonated
form
Ruhemann's
purple
(PRP)
has
been
developed.
Both
3-substituted
and
3,3-disubstituted
reacted
with
PRP,
affording
corresponding
3-azabicyclo[3.1.0]hexane
cycloadducts
in
moderate
good
yields
high
diastereofacial
selectivity.
Moreover,
several
unstable
1,2-disubstituted
were
successfully
trapped
by
1,3-dipole
under
mild
conditions.
The
mechanism
PRP
thoroughly
studied
using
density
functional
theory
(DFT)
methods
at
M11/cc-pVDZ
level
theory.
have
found
be
HOMO
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(21), P. 13202 - 13202
Published: Oct. 30, 2022
The
possibility
of
generating
azomethine
ylides
from
11H-benzo[4,5]imidazo[1,2-a]indol-11-one
and
amino
acids
is
shown
for
the
first
time.
Based
on
cycloaddition
reactions
these
with
cyclopropenes
maleimides,
cyclopropa[a]pyrrolizines,
3-azabicyclo[3.1.0]hexanes,
pyrrolo[3,4-a]pyrrolizines
spiro-fused
a
benzo[4,5]imidazo[1,2-a]indole
fragment
were
synthesized.
Spirocyclic
compounds
obtained
in
moderate
to
good
yields,
albeit
poor
diastereoselectivity.
Density
functional
theory
calculations
performed
obtain
an
insight
into
mechanism
1,3-dipolar
11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived
cyclopropenes.
cytotoxic
activity
some
cycloadducts
against
human
erythroleukemia
(K562)
cell
line
was
evaluated
vitro
by
MTS-assay.
