Cyanogenic Glycosides - Philadelphia University · 2018-11-19 · They are O-glycosides...
Transcript of Cyanogenic Glycosides - Philadelphia University · 2018-11-19 · They are O-glycosides...
1
Learning Outcomes:
❖ Definition of saponins
❖ Classification of saponin
❖ Properties of saponins
Dr. Pran Kishore Deb
Dr. Balakumar ChandrasekaranAssistant Professor
Pharmaceutical Medicinal Chemistry
Faculty of Pharmacy, Philadelphia University-Jordan
Email: [email protected]
Cyanogenic Glycosides: Part-1
Cyanogenic Glycosides
PART-1
Learning Outcomes
▪ At the end of this lecture students will be able to
❖ Define cyanogenic glycoside
❖ Outline natural occurrence of cyanogenic glycosides
❖ Define cyanogenesis
❖ Explain the significance of cyanogenic glycoside
❖ Explain the botanical name, family name and uses of
important plants species containing cyanogenic glycosides
2
▪ They are O-glycosides (ꞵ-linked) yielding HCN gas on hydrolysis
▪ Cyanogenic glycosides are represented by >2500 species
▪ Common plant Families
▪ Rosaceae, Leguminoseae, Gramineae, Araceae, Poaceae, Compositeae,
Euphorbiaceae, and Passifloraceae
▪ Common plant genera reported to cause poisoning
▪ Prunus spp. (wild cherry, black cherry, choke cherry, bitter almond)
▪ Sambucus spp. (elderberry, Linum (flax))
▪ Sorghum spp. (sorghum, sudan grass, Johnson grass)
▪ Manihot (cassava)
▪ Bambusa (bamboo)
▪ Triglochin spp. (arrow grass) 3
Cyanogenic/Cyanophore Glycosides
▪ Cyanogenic glycosides are widely distributed among 100 families of
flowering plants
▪ They are also found in some species of ferns, fungi and bacteria
▪ Many economical important plants are highly cyanogenic
▪ White clover, linum, almond, sorghum, rubber tree and cassava roots
▪ Volatile oils of bitter almond & wild cherry are used as sedatives
▪ In various cough syrups and similar preparations
4
Natural Distribution of Cyanogenic Glycosides
5Bird cherry
Sorghum Cassava Root
Lima beans
Almonds
White clover
▪ Cyanogenesis - ability of plants to synthesize cyanogenic glycosides
▪ Plants protective mechanisms against predators (herbivores)
▪ Cyanogenic glycosides - responsible for multiple disease conditions
▪ Both in animals and people
▪ Account for ≈90% of the wider group of plant toxins (cyanogens)
▪ They are condensation products of HCN and carbonyl compounds
▪ Producing cyanohydrin (unstable) - Aglycon
▪ Glycosylation (mostly D-glucose) gives cyanogenic glycosides
(stable)
6
Cyanogenic/Cyanophore Glycosides
▪ More than 50 cyanogenic glycosides have been identified
7
Cyanogenic/Cyanophore Glycosides
▪ Enzyme hydrolysis of cyanoglycosides releases cyanohydric acid (HCN)
▪ β-glucosidase hydrolyses cyanoglycosides - cyanohydrin and sugar
▪ Hydroxynitrile lyase decomposes cyanohydrin - HCN & ketone/aldehyde
8
Cyanogenic/Cyanophore Glycosides
▪ If the plant tissue is intact
▪ Enzyme (cytosol) and cyanogenic glycoside (vacuoles) remain separated
▪ If the plant tissue is damaged
▪ Enzyme and cyanogenic glycoside are put in contact
▪ Cyanohydric acid (HCN) is released
▪ Cyanohydric acid is extremely toxic to a wide spectrum of organisms
▪ Due to its ability to link with metals (Fe++, Mn++, Cu++) that are
functional groups of many enzymes
▪ Inhibit the reduction of oxygen in the cytochrome respiratory chain
▪ Inhibit the electron transport in the photosynthesis, and
▪ Inhibit the activity of enzymes like catalase, oxidase
▪ Amount of cyanogenic glycosides production dependents on
▪ Age, variety of the plant and environmental factors
9
Toxixity of Cyanogenic Glycosides
▪ Botanical name: Manihot esculenta
▪ Family – Euphorbiaceae
▪ Part of the plant used – Root
▪ 5 to 10 cm in diameter at the top
▪ Around 15 to 30 cm long
▪ In Spanish and US - called as YUCA
▪ Cassava (dried powdery) - called TAPIOCA
▪ Fried, granular form - called GARRI
10
CASSAVA
GARRI TAPIOCA
CASSAVA ROOT
▪ Cassava is the third-largest source of food carbohydrates in tropics,
after rice and maize
▪ One of the major staple food in the developing world
▪ Providing a basic diet for over half a billion people.
▪ It is one of the most drought-tolerant crops
▪ Nigeria - world's largest producer; Thailand - largest exporter of cassava
11
CASSAVA
▪ Cassava roots, peels and leaves should not be consumed raw
▪ Contain two cyanogenic glucosides - linamarin and lotaustralin
▪ Sweet cassava root = Cyanogenic glucosides are less (20 mg/kg of fresh roots)
▪ Bitter cassava root = Cyanogenic glucosides are more (1g/kg of fresh roots)
▪ A safe processing method known as the "wetting method"
▪ Mix the cassava flour with water into a thick paste
▪ Then let it stand in the shade for five hours
▪ West Africa - peel the roots and put them into water for 3 days to ferment
12
Cassava
▪ Raw consumtion of cassava diets – causes Linamarin absorption
▪ Causes inhibition of Na-K-ATPase
▪ Giving rise to electrolyte imbalance with potassium depletion
▪ Causing cellular swelling, vacuolation and rupture of the epithelial
cells of the proximal tubules
▪ Results in proteinuria and low serum albumin concentration
▪ Symptoms of acute cyanide intoxication
▪ Appear four or more hours after ingesting raw or poorly processed cassava
▪ Vertigo, vomiting, and collapse - death may result within 1-2 hours
▪ Nigeria 1989 - Eight patients died shortly after eating a meal of gari
▪ Chronic, low-level cyanide intoxication
▪ Development of goiter and tropical ataxic neuropathy
▪ lesions of skin, mucous membranes, optic and auditory nerves, spinal
cord and peripheral nerves
▪ In late-2010s, dozens of deaths were reported due to Venezuelans
▪ Due to eating bitter cassava in order to curb starvation
▪ KONZO is an epidemic paralytic disease
▪ Occurring among hunger-stricken rural populations in Africa
▪ Due to intake of insufficiently processed cassava diet
▪ Results in simultaneous malnutrition and high dietary cyanide intake
▪ Affects the legs more than the arms
▪ The resulting disability is permanent but does not progress
▪ Konzo was first described by Giovanni Trolli in 1938
▪ Compiled from the observations of eight doctors working in the Kwango
area of the Belgian Congo (Now Democratic Republic of the Congo)
Amygdalin
▪ Found in bitter almond (Prunus dulcis)
▪ kernels (nuclei) of fruits like peaches, apricot, cherries, plums
▪ Family: Rosaceae
Peaches PlumsApricot
Almonds
Hydrolysis of Amygdalin
▪ Emulsin (enzyme) – present in kernals of almond
▪ Mixture of 2 enzymes - amygdalase and prunase
▪ Mandelonitrile: 2 types (D & L configurations)
▪ Configurations in relation to mandelic acid
▪ Amygdalin containing drugs - also classified as aldehyde glycosides
▪ Since one of the products is benzaldehyde
• Dried stem bark of Prunus serotina
• Family: Rosaceae
• The plant is indigenous to USA and Canada.
• This plant was used by the red Indians as a domestic medicine
• It contains
• D-mandelonitrile glucoside (prunasin)
• Emulsin
• β-methyl aesculetin (methylether of dihydroxy coumarin).
• L-mandelic acid and p-coumaric acid, trimethylgallic acid.
• The HCN acid liberated from this plant
• Inner bark ≈ 0.23 - 0.32%
• Outer bark ≈ 0.03%
• Uses: Used as syrup, flavoring agent, sedative expectorant
Wild Cherry
Sambucus nigra
▪ Contains L-mandelonitrile glucosideknown as sambunigrin, in the leavesof the plant
Prunus laurocerasus
◼ Contains D and L-mandelonitrile
glucoside known as Prulaurasin, in
the leaves of the plant
Typical levels for some plant materials consumed by humans are:
Cyanogenic/Cyanophore Glycosides
1. Kip E. Panter. Chapter 64 - Cyanogenic Glycoside-Containing
Plants. In: Ramesh C. Gupta (Ed.). Veterinary Toxicology, Basic
and Clinical Principles. 3rd Edition, Academic Press, 2018, 935-940.
2. Janos Vetter. Plant cyanogenic glycosides. Toxicon 2000, 38, 11-36.
3. P. Kakes. Properties and functions of the cyanogenic system in
higher plants. Euphytica 1990, 48, 25-43.
4. Boivin MJ, Okitundu D, Bumoko GMM, Sombo MT, Mumba D,
Tylleskar T, Page CF, Tamfum Muyembe JJ, Tshala-Katumbay D.
Neuropsychological effects of KONZO: a neuromotor disease
associated with poorly processed cassava. Pediatrics. 2013,
131(4), e1231–e1239.
REFERENCES