Phenolic and Anthracene glycosides

1. Phenolic and Anthracene Glycosides
Ph.D.Ahmed Metwaly
Email: ametwaly@azhar.edu.eg
• Associate Professor of Pharmacognosy , Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
• Associate Professor, Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology
Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt
• Senior research fellow, Liaoning University of Traditional Chinese Medicine, China (20118-2019)
• Visiting scholar, School of Pharmacy, University of Mississippi, USA (2012-2014)

2. OBJECTIVES:
1. Phenolic Glycosides
2. Anthracene Glycosides

3. Phenolic Glycosides

4. PHENOLIC GLYCOSIDES

5. A-SIMPLE PHENOLIC GLYCOSIDES
1- Arbutin (Hydroquinone glucoside)
⮚ Occurrence: It occurs in the dried leaves
of Uva ursi ‫ب‬‫عن‬
‫الدب‬ (Ericaceae).
⮚Chemical tests
Arbutin+ FeCl3 Blue color.
⮚Hydrolysis:

6. ACTION AND USES:
1) Skin whitening
Arbutin produced a concentration-dependent inhibition of melanin synthesis of human melanoma cells
1) Formerly used in urethritis and cystitis.
2) Urinary tract Antiseptic.
3) Inflammation of prostate

7. OCCURRENCE:
IN THE LEAVES OF
GAULTHERIA PROCUMBENS L. (WINTERGREEN) ‫عنب‬
‫رض‬‫أ‬‫ل‬‫ا‬
AND BARK OF MONOTROPA FAM. ERICACEAE.
B- Phenolic and ester glycosides
Gaultherin and Monotropin

8. ▪ The sugar part is the disaccharide primeverose (glucose and xylose) in case of gaultherin
and glucose in case of monotropin.
▪ Uses: Antipyretic, Analgesic and antirheumatic
/ acid
primeverose

9. C-PHENOLIC AND ALCOHOLIC GLYCOSIDES
1- Salicin (O- hydroxyl benzyl glucoside)
Occurrence
Salicin is found in Salix fragilis ‫صفصاف‬
‫الهش‬ , and in Populus spp.
Hydrolysis
Uses:
Antirheumatic, antipyretic in case of fever and analgesic
Salicin+ conc. H2SO4 → red color + H2O → no red color.
Chemical tests:

11. Oxidation
Salicin is a pro-drug that is gradually transported to the lower part of the intestine, hydrolysed to
saligenin by intestinal bacteria, and converted to salicylic acid after absorption.
It thus produces an antipyretic action without causing gastric injury

12. 2- POPULIN:(BENZOYLSALICIN)
Occurrence
It is a sweet glycoside isolated from Populus tremula.
Hydrolysis
Uses
It is used as analgesic, antipyreticand anti-inflammatory.

13. 3- CONIFERIN
(M- METOXY, P- HYROXY CINNAMYL ALCOHOL GLYCOSIDE)
Occurrence:
It is found in the cambium tissues of pine trees
Uses:
Coniferin and coniferyl alcohol were used as starting material for
semisynthesis of vanillin

14. Anthracene
glycosides

15. ⮚They occur as pharmacologically active constituents of
several cathartics of plant origin
Senna Cascara
Rhubarb Frangula
Aloe

16. ▪Oxidation could be achieved by using H2O2/ FeCl3.
▪Reduction is carried out by using Zn dust / acetic acid or SnCl2 / HCl.

17. Types of anthraquinone glycoside
1. O-glycosides where the aglycone moiety is 1,8
dihydroxy anthraquinone derivatives, e.g.,
2. O-glycoside where the aglycone moiety partially reduced
1,8 dihydroxy anthraquinone, e.g., Oxanthrone-type.

18. 3. C-glycoside where the aglycone structure (anthrone.)
aloin
4. O-glycosides where the aglycone moiety is di-anthrone. (i.e.,
dimmer) e.g., Sennosides where there is C-C bridge between the
anthranol units. Sennoside A&B

19. ANTHRACENE GLYCOSIDES
❖Pharmaceutical importance
✔Anthracene glycosides are oxygenated derivatives of pharmacological importance that are used as laxatives or
cathartics, anti-inflammatory, antibacterial, antifungal and also as natural dyes.
⮚They are stimulant cathartics and exert their action by:
1)Increasing the tone of the smooth muscle in the wall of the colon.
2)Stimulating the secretion of water and electrolytes into the large intestine.
⮚Glycosides of anthranols and anthrones have a more drastic action than the corresponding anthraquinone.
⮚Anthraquinone drugs must be stored for at least one year before their use or heated for one hour at 100°C.

20. Tests for Identification of anthracene glycosides
1. Micro sublimation test for free anthraquinones:
Drugs containing free anthraquinones give on microsublimation needle-like crystals which give
a characteristic red color with alkali.
2. Bornträger's test for anthraquinone glycosides:
▪ The powdered drug (0.1g) is boiled for 2 minutes with about 5 ml of dilute acid (hydrolysis
of glycosides)
▪ Filter and cool (aglycones are soluble in hot but not in cold water)
▪ Shake the filtrate with an immiscible organic solvent (benzene, ether or chloroform).
▪ Separate the organic layer (anthraquinone aglycones) and shake vigorously with
ammonium hydroxide (10 %); the aqueous layer becomes rose pink or cherry red
immediately

21. Modified Bornträger's test:
▪ Addition of oxidizing agents such as a drop of H2O2 will speed the oxidation process.
▪ Anthranol glycosides should, therefore, be subjected to a process of oxidative hydrolysis to give a
positive response.
▪ In case of dianthrones (such as sennosides), the powdered drug is boiled with alcoholic KOH
(hydrolysis, formation of K salts of aglycones and H2O2 to cleavage of the C-C linkage) and filtered. The
filtrate is treated with dilute HCl (acidification), extracted with ether and the ethereal layer treated with
ammonia; a rose-red to intense red color is produced in the aqueous layer.

22. Sol. In organic solvent
NH4OH

23. Insol. In organic solvent
NH4OH
Sol. In organic solvent
NH4OH
Acid Hydrolysis
HCl
1- Borntraeger’sTest

24. Insol. In organic solvent
NH4OH
Sol. In organic solvent
NH4OH
Oxidative Acid Hydrolysis
HCl + H2O2
2- Modified
Borntraeger’sTest

25. I. Anthraquinones
Anthraquinone is a tricyclic structure which has weak
reducing properties

26. Rhein glucoside
Diacerin (1-8 Diacetyl Rhein)

27. Metabolism of anthraquinone glycosides
1- Metabolism of Rhein–8-O-β-D-glucopyranoside
⮚ Rhein–8-O-β-D-glucopyranoside is hydrolyzed to rhein (by the effect of intestinal
bacterial β-glucosidase enzyme) and then reduced and transformed to rhein anthrone
that is the final laxative principle of both rhein and its glucoside.
✔ Note: Rhein or rhein glucoside by themselves are not effective as laxative.
rhein anthrone
1. intestinal bacterial β-glucosidase
Rhein
2. intestinal bacteria reduction

28. 2- Metabolism of Diacerein (Synthetic 1-8 Diacetyl Rhein)
1- When absorbed from the upper intestine to the blood stream it exerts an anti-inflammatory
activity.
2- The non-absorbed part of rhein undergoes reduction to rhein anthrone in the large intestine
by the effect of intestinal bacteria and acts as laxative (this pathway leads to diarrhea in some
of the patients taking diacerein).
▪ Diacerein exerts both analgesic and anti-inflammatory
activities, and is used for the treatment of osteoarthritis.
▪ Diacerein is deacetylated by intestinal bacteria to yield
rhein, which is the active compound and produces two
different effects according to the site of absorption:

30. (Mechanism of action)
Diacerein's active metabolite rhein
• Rhein reduces cartilage destruction by decreasing expression and activity of matrix metalloproteinase
(MMP)-1 and -3.
• The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large
role in reduction of extracellular matrix production, MMP activity, and continued inflammation .
• Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism
Toxicity
Rhein has an oral LD50 of >5000mg/kg in mice.This is equivalent to a diacerein dose of >6476mg/kg.

32. Some aglycones of common anthraquinone
glycosides are:
1-Alizarin: (1, 2-dihydroxy anthraquinone)
In the roots of madder plant, Rubia tinctoria, Fam. Rubiaceae.
It was known and used by Ancient Egypt, Persia and India.
In 1869, it became the first natural dye to be produced
synthetically
Uses:
Laxative
Alizarin Red is used in a biochemical assay to determine,
quantitatively by colorimetry, the presence of calcific
deposition by cells of an osteogenic lineage

33. Properties
▪Carminic acid is an anthraquinone C-glucoside.
▪It is soluble in water and alcohol.
Uses
▪In color photography and painting.
▪As a natural color for foods and drugs.
▪As a stain for bacteria.
2- Carminic acid
Occurrence
Red pigment present in scale insect
(Cocchineal), Coccus cact

34. 3-The emodins:
a- Frangula emodin (emodin) : 1,6,8- Trihydroxy - 3-
methyl anthraquinone
It occurs as the rhamnoside frangulin in Rhamnus Spp, Cascara sagrada, Fam. Rhamnaceae
Uses: laxative

35. b-Aloe-emodin:
Occurance: as free and combined in rhubarb, senna, cascara and aloes
Uses: Cathartic

36. 4-CHRYSOPHANOL:
1.8- DIHYDROXY -3- HYDROXY METHYL ANTHRAQUINONE.
IT OCCURS IN THE BARKS OF CASSIA, RUMEX SPP,
CASCARA, FRANGULA AND RHUBARB.
USES
*IT IS USED FOR COMMERCIAL PRODUCTION OF CHRYSAROBIN BY REACTING
CHRYSOPHANOL WITH ZN DUST/ACETIC ACID.
*IT IS ALSO USED AS ANTIMICROBIAL AND CATHARTIC AGENT.

37. 5-RHEIN:
Isolated from Rhubarb
rhizomes, Rheum palmatum,
Fam. Polygonaceae
Uses: Laxative

38. • Bone and joint: Decreases inflammation and cartilage destruction and also corrects altered osteoblast
acitivity.
• Lipid lowering and anti-obesity: Reduces body weight and fat content, and lowers high density
lipoprotein and low density lipoprotein
• Anti-cancer: produced DNA damage and suppress DNA repair in cancer cells. induced apoptosis via ER
stress, calcium, and mitochondria mediated pathways. Rhein also prevents cancer cell invasion into
systemic circulation by preventing angiogenesis. Finally, rhein suppressed the activation of several tumor
promoting signalling pathways.
• Anti-inflammatory: Suppresses the production of pro-inflammatory cytokines such as interleukin-
1beta and interleukin-6.
• Anti-microbial: Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori . Rhien also
appears to be effective against many genotypes of Staphylococcus aureus .
• Anti-allergenic: Inhibits production of leukotrienes and the release of histamine from mast cells

40. II- ANTHRANOLS AND ANTHRONES.
•These are reduced anthraquinones (free or combined).
•Oxidation of these compounds may take place during storage of
specially powdered crude drugs.
Chrysarobin Barbaloin (Aloin)
1) Antipsoriatic for the treatment of
skin diseases, but may cause renal
damage.
2) It has antifungal and keratolytic effect.
⮚ It is a mild laxative C-glucoside isolated
from Aloes.
⮚ Barbaloin by itself is not laxative but
must be transformed first to aloe-emodin
anthrone that is the intestinal bacterial
metabolite responsible for the laxative
effect of barbaloin.

41. III. DIANTHRONES
1- SENNIDINS (SENNOSIDES A, B, C AND D):
- They are the aglycones of sennosides which are the
main glycosides of Senna leaves and pods.
▪ Sennoside A is insoluble in water, while sennoside B is
water-soluble (can be used for separating a mixture of A & B).
c meso
meso

42. 1.Similar anthrone moiety (Homo-dianthrones) i.e., 2 rhein anthrone
moieties condensate through two C-10 atoms. Thus it can be exist in
two optical forms, Sennoside A (L- form) & Sennoside B (meso form).
Sennosides A &B
2.Different (Hetero-dianthrones) i.e., one rhein-anthrone & one
emodin anthrone, Sennoside C (L- form) and Sennoside D (meso
form).
Sennoside C&D

43. Uses:
1. Senna used as laxative for habitual (acute) constipation, it stimulates the
muscular coat of the large intestine & produces purgation.
2. Used in slimming herbal tea.
3. X-ray investigation.
4. After hemorrhoids surgery.
Contraindication:
1. Pregnant women.
2. Lactating mother.
3. Inflammatory conditions of the alimentary tract.
4. Children (under 10)
5. Intestinal obstruction.
6- Sever dehydration
7- Chronic constipation

44. 2- Hypericin
Occurrence
▪It is isolated from the flowering tops of
Hypericum perforatum (st. john’s warts).
▪It is aromatic polycyclic dianthrones.
Uses
Hypericin is used as tranquilizer, antidepressant
(MAO inhibitor), and antiviral (anti-HIV).
Caution: Hypericin is a photosensitizing agent,
so avoid sunray (UV) and solarium treatment,
especially in people with fair skin.

45. Ph.D.Ahmed M.Metwaly
Associate professor,Pharmacognosy
department,
Faculty of Pharmacy,Al-Azhar University.
ametwaly@azhar.edu.eg
Email: ametwaly@azhar.edu.eg 45