Transcript - ISpatula

Aloe spp (Liliaceae)
• Aloe barbadensis, A. ferox dried juice from the leaves
OH
O
(from leave base)
OH
8
1
9
• Strong purgative
3
10
• Barbaloin A & B (stereoisomers)
CH OH
Glucose
H
• Aloenosides A & B (stereoisomers)
Barbaloin
• Aloin= H2O-sol. components of aloe
OH
O
OH
Aloin might be used for barbaloin
8
1
2
9
Best avoid aloin (ambiguous term)
3
10
H
11
CH2OR
Glucose
Aloenoside:
R= Rhamnose
1
Aloe barbadensis (Curacao aloes)
2
Aloe vera
3
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
4
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
1. COOH-free anthraquinones e.g. chrysophanol, aloe-emodin,
emodin & physcion
2. COOH-containing go e.g. rhein
3. Anthrones & dianthrones of the above
4. Hetero-dianthrones of anthrones 1 & 2
OH
8
O
OH
1
9
6
(Aloe-Emodin)
3
10
CH2OH
10'
HO
(Emodin)
(Chrysophanol)
OH
O
OH
Palmidin A
• Tannins of rhubarb responsible for mild activity
5
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).
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Rheum palmatum
7
Rhubarb (Rhei Radix) Biologically active
anthraquinones
OH
8
O
OH
8
OH
1
O
OH
1
9
9
6
(Aloe-Emodin)
3
10
CH2OH
3
10
COOH
10'
HO
O
Rhein
(Chrysophanol)
(Emodin)
OH
O
OH
OH
O
OH
Palmidin A
9
10
R2
R1
O
Chrysophenol R1= CH3
R2= H
Aloe-emodin R1= CH2OH R2= H
Physcion
R1= CH3
R2= OCH3
8
Raponticin: A stilbene glucoside from Rheum raponticum,
R. undulatum; estrogenic action, treatment of menopausal
symptoms; Alzheimer’s disease(?)
9
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
Glucose
Glucose
O
O
O
OH
OH
O
OH
8
9
10
H
H
H
COOH
9
H
9
10
Glucose
O
O
Sennoside A
OH
O
O
OH
Sennoside B
OH
1
9
3
COOH
10
COOH
10
Glucose
COOH
O
COOH
O
Rhein
10
Cassia senna
Cassia angustifolia
11
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
12
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
13
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)
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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, ….)
Biosynthetic Steps:
1 AcetylS-CoA + 6 MalonylS-CoA → Polyketide →
Griseophenone C →B →A →Dehydrogriseofulvin →
Griseofulvin
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!
Tetracyclines
R4 R3
8
9
7
R2
6
R1
NH(CH3)2
OH
5
H
10
OH
4
OH
N
1
O
OH
O
O
R5
Tetracyclines
Naturally occurring: Tetracycline, Chlorotetracycline, Oxytetracycline
Semi-synthetic: Doxycycline, Meclocycline, Methacycline, Minocycline,
Tigecycline,…
Pharmacological Properities of
Tetracyclines
R4 R3
8
9
7
R2
6
R1
NH(CH3)2
OH
5
10
OH
4
OH
H
N
1
O
OH
O
O
• 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
R5
• 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] →Polyketo-acid →condensation →Erythronolide ring (14 atoms)→glycosidation
→Erytrhromycine
[ 1 CH3-CH2-CO-SCoA + 6 HOOC-CH-(CH3 )-CO-SCoA ]
Macrolide stability
• Erythromycin is unstable under acidic conditions
• Degradation to inactive compounds by a process initiated by the 6hydroxyl 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
Nystatin A1