Anthracene (Anthraquinone) Anthracene (Anthraquinone) GlycosidesGlycosides

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

also as natural dyes.also as natural dyes.

1

4

9

10

8

5

Anthraquinone

Reduction

Oxidation

OxanthroneAnthrone

O

O

O

OHH

O

HH

Oxidation

Anthranol

OH

tautomerization

Reduction

The activity decreases as oxidation level increase.The activity decreases as oxidation level increase.

Forms of Anthracene derivatives in Forms of Anthracene derivatives in Plants:Plants: Aglycones:Aglycones:

OH OH

CH3HO

O

O

OH OH

CH2OH

O

O

OH OH

CH3

O

O

OH OH

COOH

O

O

RheinChrysophanolEmodin Aloe-emodin

Dimeric Anthracene derivatives:Dimeric Anthracene derivatives: They are derived from two anthracene unites connected by They are derived from two anthracene unites connected by

covalent C-C bond through C-10.covalent C-C bond through C-10.

Homo-Dianthrones:Homo-Dianthrones: The two anthrone moieties are similar. e.g. Sennidins A&B The two anthrone moieties are similar. e.g. Sennidins A&B

and their corresponding glycosides Sennosides A&B. They and their corresponding glycosides Sennosides A&B. They are all formed of two Rhein monomers. The A group are (l)-are all formed of two Rhein monomers. The A group are (l)-form while the B group are meso compounds with zero form while the B group are meso compounds with zero optical rotation.optical rotation. OR OH

COOH

O

OROH

HOOC

O

HH

R= H Sennidin A

R= Glc Sennoside A

R= H Sennidin B

R= Glc Sennoside B

=

=

=

=

Hetero-Dianthrones:Hetero-Dianthrones: The two anthrone moieties are different. e.g. Sennidins C&D The two anthrone moieties are different. e.g. Sennidins C&D

and their corresponding glycosides Sennosides C&D. They and their corresponding glycosides Sennosides C&D. They are all formed of one Rhein and one Aloe-emodin monomers. are all formed of one Rhein and one Aloe-emodin monomers. The C group are (l)-form while the D group are meso The C group are (l)-form while the D group are meso compounds with zero optical rotation.compounds with zero optical rotation.

OR OH

CH2OH

O

OROH

HOOC

O

HH

R= H Sennidin C

R= Glc Sennoside C

R= H Sennidin D

R= Glc Sennoside D

=

=

=

=

Glycosides:Glycosides: O-glycosides:O-glycosides:

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

C-glycosides:C-glycosides: e.g. Barbaloin it is formed from the removal of one sugar from e.g. Barbaloin it is formed from the removal of one sugar from

Cascarosides.Cascarosides.

O OH

CH2OH

O

RR1

Glc

R= Glc, R1= H Cascaroside AR= H, R1= Glc Cascaroside B

OH OH

CH2OH

O

GlcH

Structure-Activity Structure-Activity Relationship:Relationship:

Glycosylation is essential for activity.Glycosylation is essential for activity.

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

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

activity.activity.Oxanthrones are less active than anthrones.Oxanthrones are less active than anthrones.Complete reduction of C-9 and C-10 eliminates the activity.Complete reduction of C-9 and C-10 eliminates the activity.

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

CHCH22OH > CHOH > CH33 > COOH > COOH

Some Drugs containing Anthracene Some Drugs containing Anthracene derivatives:derivatives:

SennaSenna::Leaves and pods contain Sennosides A-D.Leaves and pods contain Sennosides A-D.The C-C bond protect the anthrone from oxidation.The C-C bond protect the anthrone from oxidation.

Cascara Cascara barkbark::Contain Cascarosides A- D.Contain Cascarosides A- D.Barbaloin present as a secondary glycoside in Barbaloin present as a secondary glycoside in CascaraCascara..They are O- and C-glycosides.They are O- and C-glycosides.The C-linked glucose at C-10 protect anthrones from The C-linked glucose at C-10 protect anthrones from

oxidation.oxidation.

Aloes:Aloes:The major glycoside in Aloes is the C-glycoside The major glycoside in Aloes is the C-glycoside

Barbaloin.Barbaloin.Barbaloin is primary glycoside in Aloes.Barbaloin is primary glycoside in Aloes.The C-linked glucose at C-10 protect anthrones from The C-linked glucose at C-10 protect anthrones from

oxidation.oxidation.

RhubarbRhubarb::It is purgative only in large doses.It is purgative only in large doses.It contains high amount of tannins that It contains high amount of tannins that

have astringent effect.have astringent effect.

Frangula barkFrangula bark::Contain anthraquinone derivatives the Contain anthraquinone derivatives the

most oxidized and least active.most oxidized and least active.

Mechanism of Action:Mechanism of Action:

The glycosides are absorbed from the The glycosides are absorbed from the small intestine and re-excreted in the small intestine and re-excreted in the large intestine where they increase large intestine where they increase the motility so produce laxation.the motility so produce laxation.

Aglycones produce griping effect so it Aglycones produce griping effect so it is recommended to prescripe is recommended to prescripe antispasmodic with them.antispasmodic with them.

Chemical test:Chemical test:Borntrager’s and Modified Borntrager’s Borntrager’s and Modified Borntrager’s test:test:

For Aglycones:For Aglycones: Extract plant material with organic solvent.Extract plant material with organic solvent. Shake with NHShake with NH44OH OR KOH.OH OR KOH.

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

with organic solvent (Ether or Benzene).with organic solvent (Ether or Benzene). Separate the organic solvent.Separate the organic solvent. Shake with NHShake with NH44OH OR KOH.OH OR KOH.

For C-Glycosides:For C-Glycosides: Boil plant material with dil. HCl/FeClBoil plant material with dil. HCl/FeCl33, filter and shake with , filter and shake with

organic solvent (Ether or Benzene).organic solvent (Ether or Benzene). Separate the organic solvent.Separate the organic solvent. Shake with NHShake with NH44OH OR KOH.OH OR KOH.

Positive result indicated by Positive result indicated by Rose Red colourRose Red colour in the aqueous alkaline layer.in the aqueous alkaline layer.

HypericinHypericin Sources:Sources: Dried flowering tops of Dried flowering tops of HypericumHypericum

perforatum.perforatum. Structure:Structure: Aromatic polycyclic dianthrones.Aromatic polycyclic dianthrones. Uses: Uses: Tranquilizer, antidepressant (MAO Tranquilizer, antidepressant (MAO

inhibitor), and antiviral (anti-HIV).inhibitor), and antiviral (anti-HIV).O OHOH

Me

O OHOH

MeHOHO