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)

Aloe barbadensis (Curacao aloes)

Aloe vera

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

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)

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).

Rheum palmatum

Rhubarb (Rhei Radix) Biologically active anthraquinones (Emodin)

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(?)

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)

Cassia senna Cassia angustifolia

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

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

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)

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

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

Biosynthesis of Griseofulvin

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

Tetracyclines

Tetracyclines

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.

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

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®)

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

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.

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

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

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

Nystatin A1