cinnamoyl-coa - philadelphia university · drugs containing anthocynidins 1. ... that are...
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Cinnamoyl-CoA
(shikimate pathway) (acetate pathways)
Biosynthesis of Flavonoids
1000 times sweeter
than table sugar Bitter 48
Anthocyanidins
• The hydroxyl groups are usually found on positions 5, 7 of ring A or at 4-, (3-, 4-), on ring B and sometimes they maybe in the form of methoxy or alkoxy, and the sugar is usually attached to the OH groups to form the glycosides.
• Anthocyanins are glycosides of anthocyanidins.
• They could be found in different parts of the plant specially in cell sap (the watery fluid within the central vacuole of a plant cell).
• Many of them are diuretic, diaphoretic and some have the ability to decrease the bleeding tendency of blood vessels and to affect the permeability of the capillaries like Rutin and Hesperidin which decrease the capillary fragility.
• In plants, in addition to being flower pigments and attracting pollinating birds and insects, other suggested roles e.g. control of plant growth, inhibiting and activating plants enzymes, some have fungicidal effect and protect plant against attack by parasites.
Either (-) or (+)-catechin
49
Drugs containing anthocynidins
1. Pelargonin
• This anthocyanin glycoside is found in the flowers of Pelargonium (Family: Geraniaceae).
• It is the 3,5-O-diglucoside of pelargonidin, and it contains one hydroxyl group on the benzene ring B.
Pelargonin
Pelargonidin
50
3. Delphinidin
• It occurs in the plants Delphinium and Viola species.
• This glycoside contains 3 hydroxyl group on benzene ring B.
52
4 . Malv id in : B l u e B e r r y, B i l b e r r y, E u ro p e a n B e r r y ( Vacc i n i um m yrt i l l u s )
• Blue berry is rich in phenolic acids, flavonoids (hyperin, quercitin) and anthocynin 0.5 % such as cyanidin, delphinidin and malvidin.
Malvidin
Vaccinium myrtillus
53
Pharmacological activity:
Blue berry anthocyanins have:
1. Vascular protection.
2. Antiedemic effect.
3. Anti-inflammatory effect.
4. Clinically, it is used for eye disease such as retina bleeding risk.
5. It has a free radical-scavenging activity (Anti-oxidant).
6. It alleviates the cognitive decline occurring in Alzheimer
disease and other conditions of aging.
7. It prevents urinary tract infection.
8. It lowers cholesterol and total lipid levels. 54
Roselle (Hibiscus subdariffa : كركديه (
• The part used is the calyx (cup) of flowers, which is widely used for the treatment of hypertension.
• This is due to angiotensin-converting enzyme activity (ACE Inhibitor) due to delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside.
Delphinidin-3-o-sambubioside 55
Leucoanthocyanidins
Leucoanthocynidins are a group of water-soluble plant pigments, very closely related to anthocynidins.
They are converted to the related anthocynidins when boiled with aqueous or alcoholic HCl acid.
Chemically, they are flavan-3,4-diols like melacacidin from Acacia species.
Melacacidin
56
Catechins
• Catechins are flavan-3-ol deravatives.
• Catechin itself is 3,5,7,3’,4’ pentahydroxyflavan.
• FlavAnols (with an "a") are not to be confused with flavOnols (with an "o"), a class of flavonoids containing a ketone group.
• Catechin is found in tea {Thea senesis}.
• It has heart-protective effect.
Catechin
57
Phytoalexins
• They are antibiotics produced by plants that act as toxins against the attacking organisms.
1. Pterocarpans:
• Pterocarpans are derivatives of isoflavonoids
• found in the Fabaceae family. • Like medicarpin and pisatin.
Medicarpin 2. Rotenone:
• Is an odorless, colorless, crystalline derivatives of
isoflavone used as a broad-
spectrum insecticide, piscicide لألسماك مبيد , and
pesticide.
• Found in Derris and Lonchocarpus species of Derris
• They are insecticide.
• Roots from both plants contain 3-5 % of rotenone,
and are also used as fish poisoning material.
• They are not toxic to humans as they are
metabolized rapidly after ingestion. 58
Cyanogenic/Cyanophore Glycosides
Cyanogenic glycosides (or Cyanophore Glycosides) are O-glycosides
yielding HCN gas on hydrolysis .
Cyanogenesis is the ability of some plants to synthesize cyanogenic
glycosides.
They are condensation products of HCN to a carbonyl compounds
producing Cyanohydrin (unstable) which upon glycosylation gives
Cyanogenic glycosides (stable).
Cyanogenesis is one of the mechanisms of plant as a protective device
against predators such as the herbivores.
Cyanogenic glycosides or cyanoglycosides account for approximately
90% of the wider group of plant toxins known as cyanogens.
C
R
R
O C
R
R OH
CN
HCN
C
R
R O-Sug
CN
Glycosylation
Cyanohydrine(Unstable)
Cyanogenic glycoside(Stable)
61
Cyanogenic/Cyanophore Glycosides
Cyanogenic glycosides when enzymically hydrolyzed, release
cyanohydric acid (HCN). In most cases, hydrolysis is accomplished by
the β-glucosidase, producing sugars and a cyanohydrin that
spontaneously decomposes to HCN and a ketone or aldehyde.
The second step can also be catalysed by the hydroxynitrile lyase,
which is widespread in cyanogenic plants.
In the intact plant, the enzyme and the cyanogenic glycoside
remain separated, but if the plant tissue is damaged both are put in
contact and cyanohydric acid is released.
62
Cyanogenic/Cyanophore Glycosides
Cyanohydric acid is extremely toxic to a wide spectrum of
organisms, due to its ability of linking with metals (Fe++, Mn++
and Cu++) that are functional groups of many enzymes,
inhibiting the reduction of oxygen in the cytochrome respiratory chain
inhibiting the electron transport in the photosynthesis, and
inhibiting the activity of enzymes like catalase, oxidase. The level of
cyanogenic glycosides produced is dependent upon the age and
variety of the plant, as well as environmental factors.
Cyanogenic glycosides are widely distributed among 100 families of
flowering plants.
They are also found in some species of ferns, fungi and bacteria.
There are many economical important plants highly cyanogenic,
including white clover, linum, almond, sorghum, the rubber tree and
cassava. 63
Cyanogenic/Cyanophore Glycosides
The best known drugs derived from such glycosides are volatile oils
of bitter almond and wild cherry, both are used as sedatives,
specially in various cough syrups and similar preparations.
Wild cherry
64
Amygdalin
This glycoside is found in bitter almond
and in the kernels (nuclei) of fruits like
apricot, cherries, peaches, plums.
Family: Rosaceae.
Peaches Plums
Amygdalin
65
Hydrolysis of Amygdalin
The enzyme emulsin (obtained from almond kernals), consists of
a mixture of 2 enzymes, amygdalase responsible for the first step
and prunase for the second step.
CH
CN
O glc glc
CH
CN
O glc
AmygdalinPrunasin
(Mandelonitrile glucoside)
1-6 linkage
CH
CN
O H
Mandilonitril
CHOHCN +
Amygdalase Prunase
Since one of the products is benzaldehyde, thus amygdalin
containing drugs are classified with aldehyde glycoside group. 66
Amygdalin
We have 2 types of mandelonitrile: D & L relative configurations
in relation to mandelic acid which is used for aromatic and not for
aliphatic compounds.
The group of cyanophore glycosides are represented by
amygdalin which is found in large quantities in bitter almond, and
also by prunasin which is found in Prunus padus (Bird cherry)
Prunus padus
Mandelic acid
67
Wild Cherry:
Dried stem bark of Prunus serotina
Family: Rosaceae
The plant is indigenous to USA and Canada.
The plant was used by the red Indians as a domestic medicine and it
contains:
D-mandelonitrile glucoside (prunasin)
Emulsin
β-methyl aesculetin (methylether of dihydroxy coumarin).
It also contains L-mandelic acid and p-coumaric acid,
trimethylgallic acid.
The HCN acid liberated from this plant is between 0.23 - 0.32%
from the inner bark and 0.03% from the outer bark.
Uses: most important uses as syrup, flavoring agent, sedative
expectorant.
68
Isothiocyanate Glycosides This group of glycosides are sometimes called thiocyanate or
sulphurated glycosides where the aglycones are thiocyanates.
Thioglycosides are particularly abundant in the families Brassicaceae (also called Cruciferae) and Capparidaceae
It is believed that these glycosides protect plants against parasites.
Biosynthesis
The biosynthesis of these glycosides was proven to be from shikimic acid for the aromatic glycosides like sinalbin, while the acetate units are the precursors for the sinigrin which are found in the white and black mustard respectively.
Sinalbin in seeds of white mustard
Sinigrin in seeds of black mustard
72
OS C
O H
O H
H O
C H 2 O HN
O
CH 2
CH
C H 2
S
O K
O
O
S C
N
H 2 C CH
C H 2
M u s t e r e d o i l( a l l y l i s o t h i o c y a n a t e )S i n i s r i n
M y r o s i n a s e
74
Simple phenolic/aldehyde glycosides
This group of glycosides contains phenolic, alcoholic, or aldehyde, group as an aglycone part of glycosides.
All are derived from shikimic acid pathway.
80
ALCOHOL GLYCOSIDES
1. Salicin
It is O-hydroxy benzoylglucoside. It is found in different species of Willow bark صفصاف like the following:
1. Salix purpurea Family: Salicaceae
2. Salix fragilis Family: Salicaceae
3. Populus species.
Usually it is hydrolyzed by the enzyme emulsin to D-glucose and saligenin.
Act as an analgesic, antipyretic and anti-inflammatory agent in human body.
82
2. Popul in:
It is benzoyl salicin and is a phenolic alcoholic glucoside.
It is found in the bark and leaves of Populus species and Family: Salicaceae.
Hydro l ys i s :
1 . By a l k a l i : it gives benzoic acid and salicin.
2 . By ac i d : it gives benzoic acid, saligenin (salicyl alcohol) and
glucose.
84 P o p u l i n
3.Coniferin :
It is m-methoxy-p-hydroxy cinnamyl alcohol glycoside .
This is found in most coniferous plants الصنوبرية النباتات
Is used for preparation of vanillin.
86
Phenol Glycosides
Arbutin
Extracted from the dried leaf of Arctostaphylos uva-ursi
Family Ericaceae الخلنجية.
USES
1. The leaves of uva ursi are traditionally brewed into a tea and useful treatment option for urinary tract infections (UTIs).
2. It inhibits tyrosinase and thus prevents the formation of melanin. Arbutin is therefore used as a skin-lightening agent.
87
Its glycoside arbutin which is upon hydrolysis yields hydroquinone and glucose.
USES:
Uva ursi has antibacterial properties because of its main bioactive, arbutin.
Arbutin creates a metabolite called hydroquinone glucuronide. When this metabolite is eliminated through urine, it also prevents bacteria from adhering to tissue in the area. This is why uva ursi may be effective at alleviating UTIs. 88
Aldehyde glycosides
Glucovanillin
Fruits of Vanilla planifolia Andrews, known in Commerce as Mexican or Bourbon vanilla.
Vanilla tahitensis J. W. Moore known in commerce as Tahiti vanilla
Family: Orchidaceae
Vanilla contains Glucovanillin (avenin) as o-glycoside which upon enzymatic hydrolysis gives vanillin (aldehyde aglycone) and glucose.
Vanillin is used as a flavoring agent specially in bakery.
89
Green vanilla pods
Bitter in taste
(odourless)
Brown vanilla pods
Sweet in taste
(Vanilla odour)
At the same time, vanillin can be prepared synthetically from
isoeugenol or coniferin or guaicol as follows:
Commercial Preparation of Vanillin
CH2-CH=CH2
OH
OCH3
CH=CH-CH3
OH
OCH3
OH
OCH3
CH=CH-CH2OH
O-glc
OCH3
Eugenol
KOH
Iso-eugenol
Oxidation
Vanillin
VanillinCHCl3+ NaOH
Reflux
Guaiacol
VanillinH2SO4/K2Cr2O7
Coniferin
90
COUMARINS (Bitter principles)
Coumarin is a fragrant organic chemical compound in the
benzopyrone chemical class, which is a colourless crystalline substance
in its standard state. It is a natural substance found in many plants.
The name comes from a French term for the tonka bean, coumarou, one
of the sources from which coumarin was first isolated as a natural
product in 1820.
It has a sweet odour, readily recognised as the scent of new-mown hay,
and has been used in perfumes since 1882. Sweet woodruff,
Meadowsweet, sweet grass and sweet-clover in particular are named for
their sweet (i.e., pleasant) smell, which in turn is due to their high
coumarin content.
When it occurs in high concentrations in forage plants, coumarin is a
somewhat bitter-tasting appetite suppressant, and is presumed to be
produced by plants as a defence chemical to discourage predation. 93
Some coumarins are phytoalexins and are synthesized de novo by
the plant following infection by a bacterium or fungus.
Phytoalexins: any of a group of compounds formed in plants in
response to fungal infection, physical damage, chemical injury, or a
pathogenic process. Phytoalexins inhibit or destroy the invading
agent.
Coumarin is used in certain perfumes and fabric conditioners.
Coumarin has been used as an aroma enhancer in pipe tobaccos and
certain alcoholic drinks.
It is banned as a flavorant food additive, due to concerns regarding its
hepatotoxicity in animal models.
Coumarin was first synthesized in 1868. It is used in the
pharmaceutical industry as a precursor reagent in the synthesis of a
number of synthetic pharmaceutical agents or drugs such as
anticoagulants (similar to dicoumarol), warfarin (brand name
Coumadin) and potent rodenticides. 94
Although coumarin is widely
distributed in plants, glycosides
containing coumarin as such are
rare.
Several glycosides of hydroxylated
coumarin derivatives, however,
occur in plant materials, and none
of the hydroxylated coumarin
glycosides is of particular
medicinal importance.
Examples of these coumarin
glycosides: skimmin in Japanese
star-anise and aesculin (saponin)
in horse chestnut tree.
95
Japanese star-anise
Scopoletin
• It is a phytoalexins found in the Quassia wood (Quassia is a
collective term for 2 plants: Picrasma excelsa and Quassia amara L. Family: Simaroubaceae), stem wood of Picrasma excelsa (Picconia excelsa or Aeshrion excelsa) (Simaroubaceae).
Uses:
• It is used as antispasmodic for its uterine sedative activity.
• It also has antimicrobial activity. 96
Psoralens
• These are photosensitizing furocoumarins that occur in a number of plant families like Umbelliferae (Apiaceae), where they are a common cause of phototoxicity.
Methoxsalen: 8-methoxy psoralen (oxsoralen ®) or xanthotoxin, a constituent of cremocarps (a description of the fruit of fennel etc.) of Ammi majus Linne (Family: Umbelliferae). It is used to
facilitate repigmentation in idiopathic vitiligo (leukoderma) and
for symptomatic control of severe disabling psoriasis.
Methoxsalen may be applied topically or taken internally, and with exposure to U.V. light.
Risks are inherent in therapy with methoxsalen including carcinogenesis.
97 Psoralens Methoxsalen
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