1. Aloe spp (Liliaceae)
Aloe barbadensis, A. ferox dried juice from the leaves (from leave base)
Strong purgative
Barbaloin A & B (stereoisomers)
Aloenosides A & B (stereoisomers)
Aloin= H2O-sol. components of aloe
Aloin might be used for barbaloin
Best avoid aloin (ambiguous term)

2. Aloe barbadensis (Curacao aloes)

3. Aloe vera

4. Other Aloe Preparations
FREE FROM ANTHRAQUINONES
Aloe vera leaf mucilage from parenchymatous layer
Herbal remedy for sunburn
Marketed as herbal remedy for skin conditions such sunburn, wound, allergic dermatitis & cosmetic products
Cosmetic industry
Polysaccharides-rich material
Effect is due to increase dermal blood flow by inhibiting both thrombxane synthase & formation of vasoconstrictor thromboxane A2
The effect includes hydration and insulation of skin

5. Rhubarb radix الرواند
Dried rhizomes & roots of Rheum palmatum (Polygonaceae)
Active Ingredients: mixture of complex anthraquinone glycosides.
Summer collection (richest in AQ)
Edible rhubarb = Rheum rhaponticum
Aglycone classification
COOH-free anthraquinones e.g. chrysophanol, aloe-emodin, emodin & physcion
COOH-containing go e.g. rhein
Anthrones & dianthrones of the above
Hetero-dianthrones of anthrones 1 & 2
Tannins of rhubarb responsible for mild activity
Pyralvex℗
(Emodin)

6. Palmidin A:
Aloeemodin-Emodin bianthrone
Palmidin B:
Aloeemodin-Chrysophanol bianthrone
Palmidin C:
Emodin-Chrysophanol bianthrone
Palmidin A, B, & C are obtained from roots of Rheum palmatum (Turkey rhubarb) and from cascara (Rhamnus purshiana).

7. Rheum palmatum

8. Rhubarb (Rhei Radix) Biologically active anthraquinones
(Emodin)

9. Raponticin: A stilbene glucoside from Rheum raponticum, R
Raponticin: A stilbene glucoside from Rheum raponticum, R. undulatum; estrogenic action, treatment of menopausal symptoms; Alzheimer’s disease(?)

10. 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 market
Sennoside C= anthrone + rhein
Sennoside D= anthrone + aloe-emodin
Sennoside A (L form) and sennoside B is the (B form)

11. Cassia senna
Cassia angustifolia

12. Senna fructus Dried fruit (pods) 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

13. Medicinal Value of Anthraquiniones
Purgative by direct stimulant action on colon to stimulate peristalsis
Glycosides increase solubility and transport to the site of action
Aglycone is the active part (Anthrone is the active form)
Colon bacteria hydrolyze glycoside & reduce anthraquinone to anthrone
Anthrone-rich extracts must be stored to allow oxidation of anthrones to corresponding anthraquinones

14. Side Effects & Contra Indications
Gripping and colicky pain
Excessive laxative effect
Electrolytes imbalance esp K+ (cardiac pt??) prolonged use
Increased risk of abortion in pregnants
Excreted in mother’s milk
Hepatic & intestinal tumors (animal expr.)
Sphincter atony (Prolonged use)

15. Antibiotics derived from the acetate metabolism
1- Antibiotics with fused ring system: -Griseofulvin -Tetracyclines -[Fusidic acid] 2-Macrolide antibiotics 3-Polyene antibiotics

16. Griseofulvin: Produced by Penicillium spp (P. griseofulvum, …
Griseofulvin: Produced by Penicillium spp (P. griseofulvum, ….) Biosynthetic Steps: 1 AcetylS-CoA + 6 MalonylS-CoA → Polyketide → Griseophenone C →B →A →Dehydrogriseofulvin → Griseofulvin
116
Meta oxygens
not tetracycline – xanthone nulceus- tricyclic like anthraquinone but O in ring B
Griseofulvin

17. Biosynthesis of Griseofulvin

18. Tetracyclines Biosynthesized from 1 MalonamylCoA + 8 MalonylCoA
(1NH2-CO-CH2-CO-SCoA +8 HOOC-CH2-CO-SCoA)→C-19 Polyketide → → →cyclisation →C-6 methylation →OH at C-4 →dearomatization → 4-keto derivative → Cl- at C-7 → amination and stepwise methylation at C-4 →
hydroxylation C-6 →reduction of double bond in ring B
Biosynthesized in Streptomyces spp. (S. aureofaciens, S. rimosus,…)
Chlorotetracycline is the first to be discovered
Broad spectrum activity
Protein synthesis inhibitor
Side effects!
tetracene

19. Tetracyclines

21. Tetracyclines

22. Naturally occurring: Tetracycline, Chlorotetracycline, Oxytetracycline Semi-synthetic: Doxycycline, Meclocycline, Methacycline, Minocycline, Tigecycline,…
A new generation of tetracyclines known as glycylcyclines has been developed to counter resistance and provide higher antibiotic activity. The first of these in general use is tigecycline. Tigecycline maintains antibiotic spectrum and potency, whilst overcoming resistance arising from both ribosomal
protection and efflux mechanisms.
(Figure 3.100), a glycylamido derivative of minocycline.

23. Pharmacological Properities of Tetracyclines
Amphoteric compounds;
Orally bioactive
Chelators and complex with metal ions, especially Ca, Al, Fe, and Mg
Not administered with foods such as milk and dairy products (which have a high calcium content), aluminium- and magnesium-based antacid preparations, iron supplements, etc.
Not prescribed to children and pregnant women ?
Tetracyclines are the antibiotics of choice for infections caused by Chlamydia, Mycoplasma, Brucella, and Rickettsia, and are valuable in chronic bronchitis due to activity against Haemophilus influenzae
Mechanisms of resistance: bacterial efflux and ribosome protection

24. Fusidic acid: Protein synthesis inhibitor, bacteriostatic, mainly used topically Biosynthesized in Fucidium coccineum; Highly inhibitory: Staphylococci, corynebacteria, clostridia Moderately inhibitory: tubercle bacilli, streptococci,.. Fusidic acid mainly given topically (Fucicort ® or Fucidin®)

25. Macrolide antibiotics
Synthesized from acetate units
Produced by Streptomyces spp.
Large lactone ring (12-16 atoms)
Numerous CH3 branching in lactone ring
One or more sugar units are attached through glycoside linkages; these sugars tend to be unusual 6-deoxy structures attached to the ring
Erythromycin A, B as examples
Mainly active against Gram-positive bacteria and Mycoplasma spp.; useful in pat. with penicilline allergy
Protein synthesis inhibitors
treatment of respiratory tract infections
SE: few, mainly GI symptoms

26. Erythromycin A: 1 [PropanoylCoA] + 6 [2-MethylmalonylCoA] →Poly-keto-acid →condensation →Erythronolide ring (14 atoms)→glycosidation →Erytrhromycine [ 1 CH3-CH2-CO-SCoA + 6 HOOC-CH-(CH3 )-CO-SCoA ]
These unusual 6-deoxy sugars are frequently restricted to this group of natural products.

27. Macrolide stability Erythromycin is unstable under acidic conditions
Degradation to inactive compounds by a process initiated by the 6-hydroxyl attacking the 9-carbonyl to form a hemiketal
Erythromycin formulated in Enteric coated tablets

28. Polyenes
The group of antibiotics known collectively as polyenes is characterized by a large lactone ring (20–44 membered) containing a series of conjugated double bonds.
The macrolide ring is often linked via a hydroxyl group to an aminosugar unit
The macrolide ring is probably derived from acetate and propionate.
They are often mixtures of closely related compounds.
Streptomyces are the usual producing organisms, and to date over 200 polyenes have been claimed
Candida albicans is susceptible to the polyenes
Cutaneous, intestinal and vaginal infections of Candida

29. Amphotericin B: formed of 16 acetate units ( 1 AcetylCoA + 15 MalonylCoA + 3 MethylmalonylCoA); macrolactone ring followed by glycosidation withD-mycosamine via OH at C-19
Amphoteric

30. Nystatin A1