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