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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: pdeb@Philadelphia.edu.jo

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

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▪ 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

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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)

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Cyanogenic/Cyanophore Glycosides

▪ More than 50 cyanogenic glycosides have been identified

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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

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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

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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

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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

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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

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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