Steroids

Toad poisons

Toads are dangerous amphibians. They are a common cause of

poisoning in dogs and, less commonly, they poison cats.
Toads exude a milky white toxin mostly from poison glands behind
their eyes, but elsewhere on their body as well. They squeeze this
poison onto the surface of their skin when they are under
threat. When treated roughly, they can even squirt the poison up to
two meters.
Dogs and cats are poisoned when they mouth the toad or sometimes
when the toad's poison gets into their eyes.
The toad's poison is also dangerous to humans and deaths have
occurred. Some adults have even been affected when they
absorbed the poison through cuts in their skin after handling a toad.

Prof. Dr. M. M. Matin 1

 Toads exude/secrete milky
white toxin/venom/poison
from parotid gland &/or skin

Venom (poison) is a complex

mixture of several
conjugated or free genins,
epinephrin, bufotenidine,
sterols, tryptamines & fats.
Cardiac poisons are
glycosides
But, toad poisons are esters

*Note: Poisonous amphibians produce toxins to defend themselves from predators.

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Structurally, these form ester(s) between
Suberyl arginine + bufagins (genins) → steroidal esters
COOH

+ bufotoxin
HN O (toxic steroid lactone
COOH esters)
HN NH
H2N suberyl arginine bufotalin

Thus, the milky white toxin/venom/poison exude/secrete from

parotid gland &/or skin of toads which mainly consists of esters
of suberylarginine & genins and is termed as TOAD POISONS

The biological functions of toad poisons are mainly due to the presence
of suberyl arginine

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Toad poisons
Sources
Name of the genin Name of the toad (source)
marinobufagin Bufo marinus;
Bufo rubescens
bufotalin Bufo vulgaris; Bufo bufo
cinobufagin Bufo gargarizans

Bufo marinus: The marine toad is also known as the cane toad or the
giant toad.
Marine toads tend to be around 15 cm in length although much larger
individuals have been recorded. Marine toads are known to have
poison glands which ensure that it has toxic skin. This means that if
another animal ate the marine toad, it's quite likely that it would
lead to near, if not fatal, consequences.

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 marinobufagin
Along with being used to control agricultural pests, the marine toad also has a
variety of other uses to humans around the world.
Traditionally, tribes people in South America would milk the toads for their toxin
(called bufotoxin), which was then used as arrow poison. There are also
suggestions that the toxins produced by the marine toad may have also been
used as a narcotic by the local people.
Introduced into many areas such as Australia and Hawaii to control insect pests.
Absorption of the toxins through the oral mucosa of dogs, and less often cats,
results in varying degrees of salivation, pulmonary edema, cardiac arrhythmias,
cyanosis and seizures which may culminate in death of the animal.
Marinobufagenin (marinobufagin) is a cardiotonic bufadienolide steroid.

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Bufo vulgaris: Causes excess salivation and distress if caught by a
dog. Called also common toad.

bufotalin
Bufotalin is a cardiotoxic bufanolide steroid, cardiac glycoside
analogue, secreted by a number of toad species. Bufotalin can be
extracted from the skin parotoid glands of several types of toad.
Rhinella marina (Cane toad), Rhaebo guttatus (Smooth-sided toad),
Bufo melanostictus (Asian toad), and Bufo bufo (common European
toad) are sources of bufotalin.
Bufotalin is part of Ch'an Su, a traditional Chinese medicine used for
cancer. It is also known as Venenum Bufonis or senso (Japanese).

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 Bufo gargarizans: Found in China

cinobufagin
Cinobufagin is a cardiotoxic bufanolide steroid secreted by the
Asiatic toad Bufo gargarizans. It has similar effects to digitalis and is
used in traditional Chinese medicine.

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Steroids
Saponins
A class of toxic compounds found in particular abundance in various
plant species, specifically amphipathic steroid & terpenoid
glycosides, grouped phenomenologically by the soap-like foaming
they produce when shaken in aqueous solutions are termed as
saponins.
Structurally they have one or more hydrophilic glycoside moieties
combined with a lipophilic steroid/triterpene derivative.
Examples of which are used in detergents and foam fire
extinguishers.

solanine

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Saponins
Structure & properties
▪ Saponins are glucosides with foaming characteristics.
▪ Saponins consist of a polycyclic aglycones attached to one or
more sugar side chains (hexoses, pentoses, or uronic acids).
▪ The aglycone part, which is also called sapogenin, is either
steroid (C27) or a triterpene (C30).
▪ The foaming ability of saponins is caused by the combination of a
hydrophobic (fat-soluble) sapogenin and a hydrophilic (water-
soluble) sugar part.
▪ Saponins have a bitter taste.
▪ Some saponins are toxic and are known as sapotoxin.
▪ Quinoa saponins are soluble in methanol & water. They have
strong detergent properties which form very stable foam in
aqueous solutions, and reduce the superficial tension of aqueous
solutions. They also show hemolytic activity and are in general
toxic to cold-blooded animals which obtain oxygen directly from
water.

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Saponins
Occurrence
Saponins have historically been understood to be plant-derived, but they have
also been isolated from marine organisms such as sea cucumber.
Saponins are phytochemicals which can be found in most vegetables, beans &
herbs. The best known sources of saponins are peas, soybeans etc. They are
also present in common foodstuffs such as asparagus, garlic, onion, and
spinach.
Saponins are indeed found in many plants, and derive their name from the
soapwort plant (genus Saponaria, family Caryophyllaceae), the root of which
was used historically as a soap.
Saponins are also found in the botanical family Sapindaceae, with its defining
genus Sapindus (soapberry or soapnut), and in the closely related families
Aceraceae (maples).
It is also found heavily in Gynostemma pentaphyllum (Gynostemma,
Cucurbitaceae) in a form called gypenosides, and ginseng or red ginseng
(Panax, Araliaceae) in a form called ginsenosides. Within these families, this
class of chemical compounds is found in various parts of the plant: leaves,
stems, roots, bulbs, blossom and fruit.
Commercial saponins are extracted mainly from Yucca schidigera and Quillaja
saponaria.

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Facts about Saponins
Saponins from Yucca and Quillaja are used in some beverages, such as
beer, to produce a stable foam. The detergent properties of saponins
have led to their use in shampoos, facial cleansers and cosmetic
creams.

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12
Hederagenin is a triterpenoid which is a
chemical constituent of the Hedera helix plant.

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Saponins
Uses/Applications

Health Benefits:
Saponins have many health benefits. Studies have illustrated the beneficial
effects on blood cholesterol levels, cancer, bone health and stimulation of the
immune system. Most scientific studies investigate the effect of saponins from
specific plant sources and the results cannot be applied to other saponins.
Role in plant ecology and impact on animal foraging
In plants, saponins may serve as anti-feedants, and to protect the plant against microbes and
fungi. Some plant saponins (e.g. from oat and spinach) may enhance nutrient absorption and
aid in animal digestion. However, saponins are often bitter to taste, and so can reduce plant
palatability (e.g., in livestock feeds), or even imbue them with life-threatening animal
toxicity.[4] Some saponins are toxic to cold-blooded organisms and insects at particular
concentrations.
Use in animal feeding
Saponins are used widely for their effects on ammonia emissions in animal feeding.

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Saponins constitute a structurally
highly diverse class of natural plant
defense compounds. Due to their
detergent-like structures, they can
disrupt cell membranes, cause cell
death, and ultimate kill herbivores
and pests. Despite their obvious
potential for use in plant protection,
we know surprisingly little about
Structure Activity Relationships – what determines bioa
which saponin structures are toxic
to certain herbivores, and which are
not.

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Health Benefits of Saponins
Saponins have many health benefits. Studies have illustrated the beneficial effects
on blood cholesterol levels, cancer, bone health and stimulation of the immune
system. Most scientific studies investigate the effect of saponins from specific
plant sources and the results cannot be applied to other saponins.
Cholesterol reduction
Saponins bind with bile salt and cholesterol in the intestinal tract. Bile salts form
small micelles with cholesterol facilitating its absorption. Saponins cause a
reduction of blood cholesterol by preventing its re-absorption.
Reduce cancer risk
Studies have shown that saponins have antitumor and anti-mutagenic activities and
can lower the risk of human cancers, by preventing cancer cells from growing.
Saponins seem to react with the cholesterol rich membranes of cancer cells,
thereby limiting their growth and viability. Roa and colleagues found that saponins
may help to prevent colon cancer and as shown in their article "Saponins as anti-
carcinogens" published in The Journal of Nutrition (1995, 125, 717s-724S). Some
studies have shown that saponins can cause apoptosis of leukemia cells by
inducing mitotic arrest.
Immunity booster
Plants produce saponins to fight infections by parasites. When ingested by
humans, saponins also seem to help our immune system and to protect against
viruses and bacteria.
Reduce bone loss
Studies with ovariectomized induced rats have shown that some saponins, such as
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Saponins
Sapogenin
The aglycones, or non-saccharide, portions of the family of natural
products known as saponins are called sapogenins.
Sapogenin examples are diosgenin, yamogenin & hecogenin etc.

yamogenin, a sapogenin
found in fenugreek

Sapogenins contain steroid (C27) or other triterpene (C30) frameworks

as their key organic feature. For example, steroidal sapogenins like
tiggenin, neogitogenin, and tokorogenin have been isolated from the
tubers of Chlorophytum arundinacelum.
Some steroidal sapogenins can serve as a practical starting point for
the semisynthesis of particular steroid hormones.

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Steroids
Steroid alkaloids or Azasteroids
An azasteroid is a type of steroid/sterol derivative which has one or
more of the carbon atoms in the steroid ring system replaced by a
nitrogen atom(s).
These are also invariably occur in the plant kingdom as glycosides in
combination with carbohydrate moieties.
These are found in plants of family solanaceae.
For example, Solanum tuberosum (potato) contains two important
azasteroids: (i) solanine-t and (ii) salanin-s (terpenoid).

solanine

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Azasteroids solanine-t and solasonine on hydrolysis produce sugar
molecules (glycone part) along with solanidine-t (solatubine) &
solanidine-s (solasodine), respectively.

H+/H2O

solanidine
solanine (solanid-5-en-3-beta-ol)

H+/H2O

solanidine-s
solasonine (solasodine)

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 Se
distillation
Diel’s hydrocarbon
solanidine

Se
distillation
solasodine Diel’s hydrocarbon

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Two azasteroids, finasteride and dutasteride, are used clinically as
5α-reductase inhibitors.
Some of the 6-azasteroids may prove to be useful drugs, but have yet to
reach the pharmaceutical market.

finasteride
It is sold under the brand names Proscar and
Propecia among others, is a medication used
mainly to treat an enlarged prostate or scalp
hair loss in men
dutasteride

It is sold under the brand name Avodart

among others, is a medication used primarily
to treat enlarged prostate in men. It can also
be used to treat scalp hair loss in men,
excessive hair growth in women, and as a
part of hormone therapy for transgender
women

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Azasteroids
Classification
The steroidal alkaloids may be broadly classified into two major
groups, namely:
(1) Solanum Alkaloids, &
(2) Veratrum Alkaloids
These two classes are perceived as pharmacologically important alkaloids,
and also as precursors of semisynthetic steroid derivatives.
(1) Solanum Alkaloids:
A good number of plants belonging to the natural
order Solanaceae have been found to accumulate favourably
several steroidal alkaloids based on a C27 cholestane skeleton,
such as: solasodine, tomatidine, solanidine.
These alkaloids usually occur in a wide variety of the genus Solanum, for
instance: Solanum laciniatum; S. dulcamara Linn.; S. nigrum Linn.; S.
torvum Swartz.; S. lycopersicum Linn.; (Lycopersicon exculentum Mill); S.
tuberosum; S. aviculare etc. The three above mentioned alkaloids
normally occur naturally in the plant as their corresponding glycosides.

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(2) Veratrum Alkaloids
The Veratrum alkaloids represent the most important and medicinally
significant class of steroidal alkaloids. It is, however, pertinent to mention
here that the basic ring systems present in the Veratrum alkaloids are not
quite the same as seen in the usual steroidal nucleus, as present either in
the cholesterol or in the aglycone residues of the cardiac glycosides.
Interestingly, (a) one may observe in the structures of Veratrum alkaloids
with regular steroidal nucleus (e.g. solanidine), and (b) the other in which
apparently is just the reverse of the pattern in the regular steroidal nucleus
i.e. ring ‘C’ is a five-membered ring while ring ‘D’ is a six-membered
ring (e.g. veratridine).

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Again, the majority of Veratrum alkaloids may be classified
into two categories solely based on their characteristic structural
features, namely:
(i) Jeveratrum alkaloids, and
(ii) Cevaratrum alkaloids

(i) Jerveratrum alkaloids: These contain 1–3 oxygen atoms, and having
antiparasitic activity (e.g. veratramine, jervine & pseudojervine etc.)

(ii) Ceveratrum alkaloids: These have a higher level of hydroxylation

(7–9 oxygen atoms), which are responsible for the hypotensive activity
of Veratrum species (e.g., germine or protoverine)

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 azasteroids

solanum alkaloids veratrum alkaloids

(solasodine, tomatidine,
solanidine etc.)
jeveratrum alkaloids cevaratrum alkaloids
(veratramine, jervine, (e.g., germine,
pseudojervine etc.) protoverine etc.)

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 Questions

Clinical & Pathological Chemistry 26

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