Anthaquinones
• Active components of many crude drugs with
purgative properties
• Colored compounds traditionally used as dyes
• Mostly glycosides (mainly glucosides or
rhamnosides)
O
• Sugar residue is prerequisite for
1
8
7
9
pharmacological effects
A
B
C
10
6
4
• 9,10-anthraquinone as basic st.
5
O
2
3
Classes of Anthraquinones
Based on degree of oxidation status
OH
Anthraquinone
O
A
9
B
10
O
red
C
O
OH
oxid
Anthrahydroquinone
oxid.
red.
oxid.
red.
OH
H
OH
Oxanthrone
O
Anthranol
H
H
Anthrone
O
oxid.
red.
H
H
O
Dianthrone
Biosynthesis of Anthraquinones
• Mainly produced via acylpolymalonate (acetatemalonate) pathway in Polygonaceae & Rhamnaceae &
Leguminosae….
• Starts with acetyl CoA carboxylation to malonly CoA
then continues in the usual way of formation of the
poly-keto-methylene-chain with simultaneous loss of
CO2 followed by cyclisation
• Shikimate-mediated in Rutaceae, Rubiaceae &
Gesneriaceae
In the biosynthesis of the anthraquinones for the formation of
the poly-keto-methylene-chain : 1 acetyl CoA and 7 Malonyl CoA
are used.
O
CH3C-S-ACP
O
O
COOH
+ 7Malonyl-ACP
O
Acetyl-ACP
COOH
O
O
O
O
Beta-Polyketo acid
OH
O
HO
OH
OH
CH3
O
OH
HO
CH3
O
Frangulaemodin
Frangulaemodin anthrone
Anthraquinones from Shikimic Acid
HO
COOH
COOH
COOH
+
HO
OH
Shikimic Acid
O
COOH
C
COOH
Alpha-Ketoglutaric Acid
O
Succinylbenzoic Acid
COOH
H3C
C
OH
O
OH
OH
OH
A
B
O
Alizarin
C
OH
HOH2C
Mevalonic acid
Important anthraquinones: OH at C-1 and C-8
R at C-3: CH3………………Chrysophanol
R at C-3: CH2OH………….Aloe-emodine
R at C-3: COOH…………. Rhein
R at C-3: CH3
and at C-6 OH Frangula-emodine
R at C-3: CH3
and at C-6 OCH3 Phycion
Natural Sources
• Widespread in plant kingdom
• Produced by microorganimsms e.g. Penicillium
& Aspergillus spp
• Anthraquinone-rich plant families:
Liliaceae, Polygonaceae, Rhamnaceae,
Rubiaceae, Fabaceae, Rutaceae
Animals produce anthraquinones e.g. cochineal
insect
Medicinal Use of Antharquinones
•
•
•
•
•
•
•
•
Purgatives
Pure compounds are rarely prescribed
Mostly used as simple extracts of crude drugs
Sugar moiety increases solubility & facilitates transport
to the site of action
Aglycone is active part
Anthrone is the most effective form
Normal flora in colon liberates aglycone to stimulate
peristalsis
Too much anthrones in crude drugs are not suitable for
use (frangula bark storing to allow {O} to anthraquinone
Frangula Bark
•
•
•
•
•
Dried bark of Rhamnus frangula L. (Rhamnaceae)
Fresh frangula rich anthrones (too strong)
Storing for one year to oxidize (mild activity and widely used)
2-4% glucofrangulins
Frangulin A & B are minor
Glucose
OH
8
O
OH
1
10
O
OH
1
9
9
6
O
8
6
3
HO
O
Emodin
6-O-Rhamnosylemodin = Frangulin A
6-O-Apiosylemodin
= Frangulin B
10
3
O
R
O
Glucograngulin A:
Glucofrangulin B:
R= Rhamnose
R= Apiose
Cascara Bark
Dried bark of Rhamnus purshiana (Rhamnaceae)
Glucose
O
8
O
Glucose
OH
1
H
O
OH
1
9
9
3
10
O
8
OR
3
R
10
R
Glucose
Cascarosides A & B :
Cascorsides C & D :
H
Glucose
R = CH2OH
R = CH3
• Cascara (Spanish word from cascara sagrada=sacred
bark)
• Fresh cascara like frangula (must be stored before
use)
• 6-9% Anthraquinones mainly Cascarosides A-D
• A & B aloe-emodine anthrone (aglycone)
• C & D chrysophanol anthrone (aglycone)
Aloe spp (Liliaceae)
• Aloe barbadensis, A. ferox dried juice from the leaves
OH
O
(from leave base)
OH
8
1
9
• Strong purgative
3
10
• Barbaloin A & B (stereoisomers)
CH OH
Glucose
H
• Aloinosides A & B (stereoisomers)
Barbaloin
• Aloin= H2O-sol. components of aloe
OH
O
OH
Aloin might be used for barbaloin
8
1
2
9
Best avoid aloin (ambiguous term)
3
10
H
11
CH2OR
Glucose
Aloenoside:
R= Rhamnose
Other Aloe Preparations
• Aloe vera leaf mucilage from parenchymatous
layer
• Herbal remedy for sunburn
• Cosmetic industry
• FREE FROM ANTHRAQUINONES
Rhubarb radix ‫الرواند‬
• Dried rhizomes & roots of Rheum palmatum
(Polygonaceae)
• Active Ingredients: mixture of complex
anthraquinone glycosides. Aglycone classification
1. Noncarboxyllated chrysophanol, aloe-emodin,
emodin & physcion
2. COOH-containing e.g. rhein
3. Anthrones & dianthrones of the above
4. Hetero-dianthrones of anthrones
OH
8
O
OH
1
9
6
(Aloe-Emodin)
3
10
CH2OH
10'
HO
(Chrysophanol)
OH
O
Palmidin A
Tannins of rhubarb responsible for mild activity
OH
Raponticin: A stilbene glucoside from Rheum raponticum,
R. undulatum; estrogenic action, treatment of menopausol
symptoms; Alzheimer’s disease(?)
Senna Folium
• Dried leaves of Cassia angustifolia or Cassia senna =
OH
O
OH
C. acutifolia (Fabaceae)
8
1
9
• Sennosides A-D
3
10
COOH
• Sennosides A & B (Homodiantrone)
O
Rhein
• Sennosides C & D (heterodianthrone)
• Sennosides A & B are ingredients of many products
in the market
Glucose
Glucose
O
O
O
OH
OH
O
9
10
H
H
H
COOH
9
H
9
COOH
10
10
Glucose
Glucose
O
O
Sennoside A
OH
O
O
OH
Sennoside B
COOH
COOH
Senna fructus
• Dried fruit of C. senna or C. angustifolia
• Same active ingredients as leaves in addition
to rhein dianthrones containing up to 10-sugar
molecules
• Milder laxative than leaves