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Flavanonols
Description
Structural
formula
1
lavanonol
or
3
1
lydioxyflavanone
or
2,3
dihydroflavonol
3-hydroxy-
2,3-dihydro-2-
phenylchrome
n-4-one
О
Taxifolin
(or
Dihydroquercetin),
Dihydrokaempferol
Flavans
CO
0
-
OH
Flavan-3-ol
(flavanol)
Catechin
(C),
Gallocatechin
(GC),
Catechin
3-gallate
(Cg),
Gallocatechin
3-
gallate
(GCg)),
Epicatechins
(Epicatechin
(EC)),
Epigallocatechin
(EGC),
Epicatechin
3-
gallate
(ECg),
Epigallocatechin
3-gallate
(EGCg)
ivan
structure
a°r°
OH
Flavan-4-ol
a°x°
OH
OH
Flavan-3,4-diol
(leucoanthocyanidin)
Anthocyanidins
Anthocyanidins
Anthocyanidins
are
the
aglycones
of
anthocyanins;
they
use
the(2-
phenylchromenylium)
ion
skeleton
Cyanidin,
Delphinidin,
Malvidin,
Pelargonidin,
Peonidin,
Petunidin
https://t.me/med1917
Isoflavonoids
Isoflavonoids
Isoflavones
use
the
3
-phenylchromen-4-one
skeleton
(with
no
hydroxyl
group
substitution
on
carbon
at
position
2
О
^ = O
Genistein,
Daidzein,
Glycitein
Isoflavanes
Other
isoflavonoidsflsoflavandiols,
Coumestans,
Pterocarpans.
Biological
activities
of
flavonoids
[44]
Flavonoids
have
been
shown
to
have
a
wide
range
of
biological
and
pharmacological
activities
in
in
vitro
studies:
anti-allergic,
anti
inflammatory,
antioxidant,
anti-microbial
(antibacterial,
antifungal,
and
anti
viral),anti-cancer,
anti-diarrheal
activities.
Antioxidant
Activity.
Flavonoids
possess
many
biochemical
properties,
but
the
best
described
property
of
almost
every
group
of
flavonoids
is
their
capacity
to
act
as
antioxidants.
The
antioxidant
activity
of
flavonoids
depends
upon
the
arrangement
of
functional
groups
about
the
nuclear
structure.
The
configuration,
substitution,
and
total
number
of
hydroxyl
groups
substantially
influence
several
mechanisms
of
antioxidant
activity
such
as
radical
scavenging
and
metal
ion
chelation
ability.
The
В
ring
hydroxyl
configuration
is
the
most
significant
determinant
of
scavenging
of
ROS
and
RNS
because
it
donates
hydrogen
and
an
electron
to
hydroxyl,
peroxyl,
and
peroxynitrite
radicals,
stabilizing
them
and
giving
rise
to
a
relatively
stable
flavonoids
radical.
Hepatoprotective
Activity.
Flavonoids
are
known
to
be
synthesized
by
plants
in
response
to
microbial
infection;
thus
it
should
not
be
surprising
that
they
have
been
found
in
vitro
to
be
effective
antimicrobial
substances
against
a
wide
array
of
microorganisms.
https://t.me/med1917
I
Invonoid
rich
plant
extracts
from
different
species
have
been
reported
I
d
possess
antibacterial
activity.
Several
flavonoids
including
apigenin,
I'liliingin,
flavone
and
flavonol
glycosides,
isoflavones,
flavanones,
mid
chaicones
have
been
shown
to
possess
potent
antibacterial
nclivity.
Antiviral
Activity.
Natural
compounds
are
an
important
source
lor
the
discovery
and
the
development
of
novel
antiviral
drugs
I
нч
-iiLise
of
their
availability
and
expected
low
side
effects.
Naturally
occurring
flavonoids
with
antiviral
activity
have
been
recognized
'.nice
the
1940s
and
many
reports
on
the
antiviral
activity
of
various
llnvonoids
are
available.
Search
of
effective
drug
against
human
immunodeficiency
virus
(HIV)
is
the
need
of
hour.
Most
of
the
work
ielated
with
antiviral
compounds
revolves
around
inhibition
of
vn
l
ions
enzymes
associated
with
the
life
cycle
of
viruses.
Structure
li
motion
relationship
between
flavonoids
and
their
enzyme
inhibitory
activity
has
been
observed.
Anticancer
Activity.
Dietary
factors
play
an
important
role
in
the
prevention
of
cancers.
Fruits
and
vegetables
having
flavonoids
I
iiivc
been
reported
as
cancer
chemopreventive
agents.
Consumption
i>l
onions
and/or
apples,
two
major
sources
of
the
flavonol
quercetin,
с.
inversely
associated
with
the
incidence
of
cancer
of
the
prostate,
lung,
stomach,
and
breast.
In
addition,
moderate
wine
drinkers
also
■.ecm
to
have
a
lower
risk
to
develop
cancer
of
the
lung,
endometrium,
esophagus,
stomach,
and
colon.
The
critical
relationship
of
fruit
and
\egetable
intake
and
cancer
prevention
has
been
thoroughly
documented.
It
has
been
suggested
that
major
public
health
benefits
could
be
achieved
by
substantially
increasing
consumption
of
these
loods.
Quercetin
is
known
to
produce
cell
cycle
arrest
in
proliferating
lymphoid
cells.
In
addition
to
its
antineoplastic
activity,
quercetin
exerted
growth-inhibitory
effects
on
several
malignant
tumor
cell
lines
in
vitro.
These
included
P-388
leukemia
cells,
gastric
cancer
cells
(FIGC-27,
NUGC-2,
NKN-7,
and
MKN-28),
colon
cancer
cells
(<
OLON
320
DM),
human
breast
cancer
cells,
human
squamous
and
pl
iosarcoma
cells,
and
ovarian
cancer
cells.lt
has
been
experimentally
proved
that
increased
signal
transduction
in
human
breast
cancer
cells
is
markedly
reduced
by
quercetin
acting
as
an
antiproliferative
agent.
https://t.me/med1917
2.3.
Galloylbergenin
from
Kazakh
traditional
medicinal
plant
of
Bergenia
crassifolia
with
anti-
lipid
droplet
accumulation
activity
[45]
Bergenia
crassifolia
(Saxifra-
gaceae)
has
been
used
for
treatments
of
bronchitis,
gastro-enteritis,
diarrhea,
hemostasia,
and
metrorrha-gia
in
Kazakh
traditional
medicine
[46].
The
phytochemical
constituents
including
bergenin,
tannins,
flavonoids,
phenols,
polysaccharaide,
and
cumarines
with
some
pharmacological
actions
such
as
antioxidant,
antimicrobial,
antiviral,
anti-inflammatory,
diuretic,
immuno
stimulating,
and
lipase
inhibiting
activities
have
also
been
reported
[47-51].
Adipogenesis
is
a
process
from
fibroblast-like
preadipocytes
to
mature
adipocytes.
Increases
in
the
mass
and
accumulation
of
lipid
droplet
of
adipocytes
are
observed
in
cases
of
severe
human
obesity
which
presents
a
risk
to
health
and
may
lead
to
the
development
of
hypertension,
hyperlipidemia,
diabetes,
and
cardiovascular
disease
under
the
number
of
pathological
disorders[52-53].
Our
research
for
novel
lead
natural
products
from
Kazakh
medicinal
plants
led
to
isolation
of
a
new
galloylbergenin,
3,1
\-di-O-
galloylbergenin
(1)
to
show
anti-lipid
accumulation
active
along
with
4,11-
t/z-O-galloylbergenin
(2)
[54],
11
-CTp-hydroxybezoyl
bergenin
(3)
[55],
(+)-catechin
3-O-gallate
(4)
[51],
and
(+)-catechin
3,5-di-O-
gallate
(5)
[56]
from
the
roots
of
B.
crassifolia.
In
this
paper,
we
describe
the
isolation
and
structure
elucidation
of
1,
and
anti-lipid
accumulation
activities
of
isolated
compounds
(Figure
2.1).
3,1
1
-
£>/-(9-galloy
Ibergenin
(1),
amorphous
powder,
[a]
D
32
-
49.6
(c
0.53,
MeOH),
showed
a
molecular
formula,
C28H24O17,
which
was
determined
by
HRESIMS
\m/z
655.0921
(M+Na)
+
],
The
presence
of
a
carbonyl
and
a
hydroxy
group
were
inferred
by
the
absorptions
observed
in
the
IR
spectrum
of
1
appearing
at
1740
and
3380
cm
1
.
https://t.me/med1917
I'lie
'H
NMR
spectrum
of
1
(Table
2.3)
suggested
the
presence
ol
a
methoxy
group
atS
H
3.9
l(s),
five
oxymethine
groups
at
S
H
I
.
’
4
(m),
5.26
(t),
4.22
(m),
4.26
(m),
and
5.14
(d),
one
aromatic
piolon
at
8
H
7.12
(1H,
s),
and
two
3,4,5-trisubstituted
benzoyl
pioupscharacteristic
signals
at
7.11
(2H,
s)
and
7.15
(2H,
s).
1:GA
H
GA
2:
GA
GA
H
3
HB
H
H
Figure
2.1.
Isolated
phenolic
compounds
from
Bergenia
crassifolia
R,
R
2
4:
GA
H
5:
GA
GA
The
gross
structure
of
lwas
deduced
from
extensive
analyses
ol
two-dimensional
NMR
data,
including
'Н-
’
Н
COSY,
HSQC,
and
IIMBC
spectra
in
CD
3
OD
(Fig.
2.2).
The
'Н-
’
Н
COSY
and
HSQC
.pectra
revealed
the
presence
of
a
partial
structure
(C-l
1,
C-2
-
C-4a,
<
I
Ob)
as
shown
in
Figure
2.2.
The
connectivity
between
aromatic
lings
and
this
partial
structure
was
revealed
by
the
HMBC
i
in
relations
of
H-lOb
to
C-2
and
C-6a,
and
H-4a
to
C-6
and
C-lOa.
I
lie
locations
of
methoxy
group
and
aromatic
proton
at
5
h
7.12
(1H,
)
were
proved
to
be
C-9
and
C-7,
respectively,
by
HMBC
correlations
of
9-OMe
to
C-9
and
H-7
to
C-6
(8
C
165.5),
C-9,
and
<
10a.
Further
analysis
of
the
]
H,
l3
C
and
2D-NMR
data
indicated
ilie
structure
of
1
was
virtually
identical
to
those
of
a
bergenin
derivative,
4,1
1
-<7z-O-galloylbergenin
(2)
except
for
difference
in
downfield
chemical
shift
of
H-3
at
5
H
5.26
(t)
and
up
field
shift
of
H-
I
nt
<S|
1
4.
19
(m)
in
1.
The
location
of
two
galloyl
groups
at
C-3
and
C-ll
of
bergenin
were
confirmed
by
'H
NMR
and
HMBC
spectra
as
shown
in
Figure
3.
I
lie
typical
downfield
shift
of
H-3
(3
H
5.26)
and
H
2
-ll
(5
h
4.64)
due
https://t.me/med1917
to
esterification
indicated
the
position
of
C-3
and
C-ll
linked
with
the
galloyl
groups(Table
l).
11
Moreover,
the
HMBC
correlations
of
H-ll
and
H-2'
to
l'-CO
(8
C
168.0),
and
H-3
and
H-2"
to
T'-CO
(8c
167.4)
also
served
to
conclude
positions
of
the
galloyl
groups
to
be
at
C-3
and
C-ll.
Figure
2.2.
Selected
2D
NMR
Correlations
for
3,11-Dz-O-galloylbergenin
(1).
The
absolute
configuration
of
1
was
determined
by
the
hyd
rolysis
of
gallate
group.
On
enzymatic
hydrolysis
with
tannase,
1
gave
gallic
acid
and
bergenin
to
confirm
the
deduced
structure.
UV
and
CD
spectral
data
of
bergenin
as
a
h
ydrolyte
of
1
was
in
good
agreement
with
authentic
sample.
Anti-lipid
droplet
accumulation
activityfor
1-5
was
evaluated.
3,11-
Dz-O-galloylbergenin
(1)
and
4,11
-dz-O-galloylbergenin
(2)
exhibited
moderate
anti-lipid
accumulation
activities
with
IC
50
values
of
38.40
pM
and
60.50
pM,
respectively.
As
a
comparison,
berberine
used
as
a
positive
control
showed
anti-lipid
accumulation
activity
with
IC
50
values
of
14.18
pM.
On
the
other
hand,
(+)-catechin
3-0-
gallate
(4)
and
(+)-catechin
3,5-di-O-gallate
(5),
which
also
possessed
one
or
two
galloyl
groups,
showed
practically
no
anti-lipid
accumulation
activity.
It
is
interesting
to
note
that
the
presence
of
galloyl
group
in
bergenin
may
play
an
important
role
to
show
anti-
lipid
accumulation
activity.
https://t.me/med1917
Table
2.3
'
I
|&
,3
С
NMR
Data
of
3,11-Dz-O-galloylbergenin
(1)
in
CD
3
OD
at
300K
a
"iS
ill
ppm
1
'l
Cl
11
i<
>11
8
H
(T,H
z
)]
S<
HMBC
•
4.24,
m
81.2
1
5.26,
t,
7=8.8
72.0
l'-CO
1
4.22,
m
73.4
III
4.26,
m
78.7
6,
10a
b
165.5
(111
119.4
/
7.12,
s
111.4
6,
9,
10a
H
H
152.4
4
142.4
III
149.3
11)11
116.8
Hill
5.14,
d,
7=10,
74.4
2,6a
11
4.25,
m,
4.67,
dd,
7=10,
6
63.7
3,
Г-СО
')
OMc
3.91,
s
61.0
9
1'
120.6
"
6
’
7.11,
s
110.4
Г-СО
5'
146.5
■1'
140.1
1'
(
()
168.0
1"
120.8
6"
7.15,
s
110.5
Г
’
-СО
1".
5"
146.6
■1"
140.3
l"-CO
167.4
Extraction
and
Isolation.The
roots
of
B.
crassifolia
were
1
siractcd
with
70%
EtOH,
and
a
part
(35
g)
of
the
extract
was
pin
lilioned
with
«-hexane,
CHCI
3
,
«-BuOH,
and
H
2
O.
The
«-BuOH
h
in-lion
was
subjected
to
an
HP-20
column
(H
2
O/MeOH,
0:1
to
1:0),
mid
(lie
80%
MeOH
fraction
(3.2
g)
was
further
separated
by
using
1111
ODS
column
(H
2
O/MeOH,
8:2
to
0:1)
to
give
5
fractions.
Г
1
actions
3-5
were
separated
by
an
ODS
HPLC
(25%
CH
3
CN/0.1%
lonnic
acid)
and
a
Sephadex
LH-20
column
(CHCl
3
/MeOH,
1:1)
to
.illbrd
3,ll-<7z-(?-galloylbergenin
(1,
7.2
mg),
4,
1
l-Jz-O-galloyl-
https://t.me/med1917
bergenin
(2,2.1
mg),
1
1-0-p-hydroxybezoyl
bergenin
(3,1.7
mg),
(+)■
catechin
3-O-gallate
(4,
2.0
mg)
and
(+)-catechin
3,5-di-O-gallate
(5,
9.5
mg).
Bergenia
crassifolia
(2.0
kg)
ext.
with
70%
C
2
H
5
OH
MeOH
ext.
(35
g/400
g)
I
Partit.with
Hexane/H
2
O
Partit
with
CH
3
CI/H
2
O
(3®1
X
g"
e
layer
|
I
Partit,
with
n-B
U
OH/H
2
O
CHCI
3
layer
|
(2.5
g)
n-BuOH
layer
(15.5
g)
H
2
O
layer
ODS
column
(5.2
g)
(MeOH/
H
2
O)
LH-20,
MeOH
HPLC,
ODS
(MeOH/
H,O)
z
A
1
3,11-cf/-O-galloylbergenin
7.2
m
2
4,11-d/-O-gailoylbergenin
2.1
mg
3
1
1-O-p-hydroxybenoylbergenin
1.7
mg
4
(+)-catechin
3-O-gallate
2.0
mg
5
(+)-catechin
3,5-d/-O-gallate
9.5
mg
Scheme
2.1.
The
extraction
and
isolation
of
B.
crassifolia
3,ll-Dr-6)-galloylbergeninl,
colorless
amorphous
powder;
[a]
D
32
-
49.6
(c
0.53,
MeOH),
IR
v
raax
(KBr)
3380
and
1740
cmUV
(MeOH)
z
max
219
(c69000),
and
278
(25400)
nm;
CD
(MeOH)
z
max
213
(A
e
-10.6),
243
(A
0),
264
(A
-2.25),
and
288
(A
4.96)
nm;
*H
and
* 1 2 3 4 5 * * * * * * *
13
C
NMR
data,
see
Table
1;
EIMS
m/z
655
M+Na
+
;
HRESIMS
[m/z
655.0921
M+Na;
calcd
for
C
28
H
2
40i
7
Na,
655.091
1].
Enzymatic
hydrolysis
of
1:A
solution
of
3,11-Dz-O-
galloylbergenin
(1,
2.00
mg)in
H
2
O
(3
mL)
was
incubated
with
tannase
(0.5
mg)
at
40°C
for
8
h.
After
evaporation,
the
residue
was
suspended
in
MeOH.
To
identify
gallic
acid
and
bergenin,
the
methanol-soluble
portion
was
subjected
to
an
ODS
HPLC
(25%
CH
3
CN/0.1%
formic
acid).
The
spectral
data
(UV
and
CD)
of
bergenin
were
compared
with
authentic
sample.
https://t.me/med1917
Pi
ohleins
I
l
.xplain:
Historically
important
natural
products,
Distribution
of
plant
resources
in
Kazakhstan.
Please
explain:
Kazakh
traditional
medicine.
I
)evelopment
condition
of
pharmacology
in
Kazakhstan?
1
Please
give
definition
for:
Natural
products
chemistry,
Natural
products,
and
Phytochemistry.
I
Illustration:
Major
classes
of
natural
products,
Definition:
Medicinal
che-
111
i
stry,
Pharmacognosy.
I
Please
making
definition
and
explain:
Metabolites,
Primary
metabolites
ami
Secondary
metabolites.
.
Please
explain:
Development
of
isolation
and
purification
of
natural
pro
ducts.
(i.
Please
make
illustration:
Phenols,
structures,
classification
and
their
biolo
gical
properties.
/.
Explain
detail:
Flavonoids,
and
their
classification,
please
show
structures
of
each
class.
К
Illustration:
Extraction
and
isolation
of
flavonoids
from
plant
resources,
and
draw
the
isolation
block
scheme,
indicate
the
applied
solvents
and
me-
I
hods.
'»
Please
discuss:
Chemical
and
biochemical
properties
of
flavonoids,
iden
tification
method.
Ill
Make
statement
on
Galloylbergenin,
structure,
distribution
in
plant
mate
rial,
isolation
and
biological
activites.
https://t.me/med1917
3.
AIKALOIDS
3.1.
Introduction,
occurrence
.nomenclature
and
classification
Introduction
Alkaloids
are
a
group
of
naturally
occurring
chemical
com
pounds
(natural
products)
that
contain
mostly
basicnitrogen
atoms.
This
group
also
includes
some
related
compounds
with
neutral
and
even
weakly
acidic
properties.
Some
synthetic
compounds
of
similar
structure
are
also
termed
alkaloids.
In
addition
to
carbon,
hydrogen
and
nitrogen,
alkaloids
may
also
contain
oxygen,
sulfur
and
more
rarely
other
elements
such
as
chlorine,
bromine,
and
phosphorus
[57].
Alkaloids
are
produced
by
a
large
variety
of
organisms
including
bacteria,
fungi,
plants,
and
animals.
They
can
be
purified
from
crude
extracts
of
these
organisms
by
acid-base
extraction.
Many
alkaloids
are
toxic
to
other
organisms.
They
often
have
pharmacological
effects
and
are
used
as
medications,
as
recreational
drags,
or
in
entheogenic
rituals.
Examples
are
the
local
anesthetic
and
stimulantcocaine,
the
psychedelic
psilocin,
the
stimulant
caffeine,
nicotine,the
analgesicmorphine,
the
antibacterial
berberine,
the
anticancer
compound
vincristine,
the
antihypertension
agent
reserpine,
the
cholinomimeticgalantamine,
the
anticholinergic
agent
atropine,
the
vasodilator
vincamine,
the
antiarrhythmia
compound
quinidine,
the
antiasthma
therapeutic
ephedrine,
and
the
antimalarial
drugquinine.
Although
alkaloids
act
on
a
diversity
of
metabolic
systems
in
humans
and
other
animals,
they
almost
uniformly
invoke
a
bitter
taste.
The
boundary
between
alkaloids
and
other
nitrogen-containing
natural
compounds
is
not
clear-cut.Compounds
like
amino
https://t.me/med1917
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