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Anthracene (Anthraquinone) Glycosides

Anthracene glycosides are oxygenated derivatives of pharmacological importance that are used as laxatives or cathartics, anti-inflammatory, antibacterial, antifungal and also as natural dyes.

O OH O

tautomerization Oxidation Reduction

H H Anthrone Anthranol H OH Oxanthrone O

8 1 9 10 5 4

O Anthraquinone

Reduction Oxidation

HO • Forms of Anthracene derivatives in

Plants:

A- Aglycones

:

OH O OH OH O OH OH O OH OH O OH CH 3 O

Emodin

O

Aloe-emodin

CH 2 OH O

Chrysophanol

CH 3 O

Rhein

COOH

The activity decreases as oxidation level increase.

B- Dimeric Anthracene derivatives

:

– They are derived from two anthracene units connected by covalent C-C bond through C-10.

1) Homo-Dianthrones: The two anthrone moieties are similar. e.g. Sennidins A&B and their corresponding glycosides Sennosides A&B. They are all formed of two Rhein monomers. The A group are

(l

) form while the B group are meso compounds with zero optical rotation.

HOOC OR O OH H H COOH OH O OR

2) Hetero-Dianthrones

:

The two anthrone moieties are different. e.g. Sennidins C&D and their corresponding glycosides Sennosides C&D. They are all formed of one Rhein and one Aloe-emodin monomers.

The C group are (l)-form while the D group are meso compounds with zero optical rotation.

OR OH O CH 2 OH H H HOOC OH O OR

– O-glycosides:

e.g. Cascarosides A & B. They are both O- and C-glycosides. Each one contain two sugar unites.

Glc O O OH CH 2 OH R 1 R – C-glycosides:

R= Glc, R 1 = H Cascaroside A R= H, R 1 = Glc Cascaroside B e.g. Barbaloin it is formed from the removal of one sugar from Cascarosides.

OH O OH H Glc CH 2 OH

Structure-Activity Relationship

:

• Glycosylation is essential for activity.

• Hydroxylation at C-1 and C-8 is essential for activity.

• Oxidation level at C-9 and C-10 is important: • Highest level of oxidation (anthraquinones) have the lowest activity.

• Oxanthrones are less active than anthrones.

• Complete reduction of C-9 and C-10 eliminates the activity.

• Substitution at C-3 have great impact on activity:

CH 2 OH > CH 3 > COOH

Some Drugs containing Anthracene derivatives:

• Senna: • Leaves and pods contain Sennosides A-D.

• The C-C bond protect the anthrone from oxidation.

• Cascara bark: • Contain Cascarosides A- D.

• Barbaloin present as a secondary glycoside in Cascara.

• They are O- and C-glycosides.

• The C-linked glucose at C-10 protect anthrones from oxidation.

•Frangula bark: Contain anthraquinone derivatives the most oxidized and least active.

• Aloes: • The major glycoside in Aloes is the

C-glycoside

Barbaloin.

• Barbaloin is primary glycoside in Aloes.

• The C-linked glucose at C-10 protect anthrones from oxidation.

OH O OH H D-glucose Barbaloin (aloin) CH 2 OH

•Rhubarb (Rhei)

:

• It is purgative only in large doses. • It contains high amount of tannins that have

astringent effect.

Mechanism of Action:

• The glycosides are absorbed from the small intestine and re-excreted in the large intestine where they cause irritation of colon mucosa increase the motility so produce laxation.

• Aglycones produce gripping effect so it is recommended to prescribe antispasmodic with them.

• Side effects: Urinary tract irritation, vomiting, diarrhea, uterine pain

Chemical test

: Borntrager’s and Modified Borntrager’s test:

• For Aglycones: • Extract plant material with organic solvent. • Shake with NH

4 OH OR KOH.

• For O-Glycosides: • Boil plant material with dil. HCl for 10 min, filter and shake with

organic solvent (Ether or Benzene).

• Separate the organic solvent. • Shake with NH

4 OH OR KOH.

• For C-Glycosides: • Boil plant material with dil. HCl/FeCl

3 , filter and shake with organic solvent (Ether or Benzene).

• Separate the organic solvent. • Shake with NH

4 OH OR KOH.

• Positive result indicated by

Rose Red colour

aqueous alkaline layer.

in the

Hypericin

• Sources: Dried flowering tops of Hypericum perforatum. • Structure: Aromatic polycyclic dianthrones.

• Uses: Tranquilizer, mild antidepressant (MAO inhibitor) • it has antiviral (anti-HIV) activity (in vitro).

OH O OH HO HO Me Me OH O OH

Side effects: allergic reaction in sensitive individuals