anthaquinones
DESCRIPTION
Anthaquinones. Active components of many crude drugs with purgative properties Colored compounds traditionally used as dyes Mostly glycosides (mainly glucosides or rhamnosides) Sugar residue is prerequisite for pharmacological effects 9,10-anthraquinone as basic st. - PowerPoint PPT PresentationTRANSCRIPT
Anthaquinones
• Active components of many crude drugs with purgative properties
• Colored compounds traditionally used as dyes • Mostly glycosides (mainly glucosides or
rhamnosides)• Sugar residue is prerequisite for
pharmacological effects• 9,10-anthraquinone as basic st.
O
O
A B C
1
2
3
45
6
78
9
10
Classes of Anthraquinones Based on degree of oxidation status
O
O
A B C9
10
O
O
A B C9
10
O
O
A B C9
10
OH
OH
red
oxid
Anthrahydroquinone
O
H OHOxanthrone
red.oxid. OH
Anthranol
O
H HAnthroneO
H H
ODianthrone
oxid.
red.
Anthraquinone
red.oxid.
Biosynthesis of Anthraquinones
• Mainly produced via acylpolymalonate (acetate-malonate) 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.
CH3C-S-ACP
O
COOH
COOHO
O O O
OOO
O OHOH
HO
Acetyl-ACP
Beta-Polyketo acid
+ 7Malonyl-ACP
CH3
Frangulaemodin anthrone
O OHOH
HO CH3
Frangulaemodin
O
Anthraquinones from Shikimic Acid
COOH
OH
HO
HO
+ C
COOH
O
COOH
Alpha-Ketoglutaric AcidShikimic Acid
COOH COOH
OSuccinylbenzoic Acid
Mevalonic acidHOH2C
COH
H3CCOOH
OH
OHO
O
OH
OH
A B C
Alizarin
Important anthraquinones: OH at C-1 and C-8R at C-3: CH3………………ChrysophanolR at C-3: CH2OH………….Aloe-emodineR at C-3: COOH…………. RheinR at C-3: CH3 and at C-6 OH Frangula-emodineR 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, RutaceaeAnimals 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
O
O
9
10
OHO
O
1
36
8Glucose
RGlucograngulin A: R= RhamnoseGlucofrangulin B: R= Apiose
O
O
9
10
OHOH
HO
1
36
8
Emodin
6-O-Rhamnosylemodin = Frangulin A6-O-Apiosylemodin = Frangulin B
Cascara Bark
Dried bark of Rhamnus purshiana (Rhamnaceae)
• 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)
O
9
10
OH
R
O
1
3
8
Glucose
GlucoseH
O
9
10
OH
R
O
1
3
8
Glucose
Glucose
Cascarosides A & B : R = CH2OHCascorsides C & D : R = CH3
OR
H
Aloe spp (Liliaceae)• Aloe barbadensis, A. ferox dried juice from the leaves
(from leave base) • Strong purgative • Barbaloin A & B (stereoisomers)• Aloinosides A & B (stereoisomers)• Aloin= H2O-sol. components of aloe
Aloin might be used for barbaloin
Best avoid aloin (ambiguous term)
O
9
10
OH
CH2OH
OH
1
3
8
Glucose
Barbaloin
H
O
9
10
OH
CH2OR
OH
1
3
8
Glucose
11
H
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 classification1. Noncarboxyllated chrysophanol, aloe-emodin,
emodin & physcion 2. COOH-containing e.g. rhein3. Anthrones & dianthrones of the above4. Hetero-dianthrones of anthrones
Tannins of rhubarb responsible for mild activity
O
9
10
OH
CH2OH
OH1
36
8(Aloe-Emodin)
O
10'
OH
HO
OH
(Chrysophanol)
Palmidin A
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 =
C. acutifolia (Fabaceae) • Sennosides A-D• Sennosides A & B (Homodiantrone)• Sennosides C & D (heterodianthrone)• Sennosides A & B are ingredients of many products
in the market
O
9
10
OH
COOH
OH
1
3
8
ORhein
O
9
10
OH
COOH
O
9
10
O
HH
COOH
O OH
O OH
COOH
O
9
10
O
H
COOH
O OH
H
Sennoside ASennoside B
Glucose
Glucose
Glucose
Glucose
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