Bufagin is a toxic steroid C₂₄H₃₄O₅ obtained from toad's milk, the poisonous secretion of a skin gland on the back of the neck of a large toad (''

Rhinella marina The cane toad (''Rhinella marina''), also known as the giant neotropical toad or marine toad, is a large, terrestrial true toad native to South and mainland Central America, but which has been introduced to various islands throughout Oceania ...

'', synonym ''Bufo marinus'', the cane toad). The toad produces this secretion when it is injured, scared or provoked. Bufagin resembles chemical substances from

digitalis ''Digitalis'' ( or ) is a genus of about 20 species of herbaceous perennial plants, shrubs, and biennials, commonly called foxgloves. ''Digitalis'' is native to Europe, western Asia, and northwestern Africa. The flowers are tubular in shap ...

in physiological activity and chemical structure. ''Bufagin'' also refers to any of several similar substances found as components of the mixture

bufotoxin Bufotoxins are a family of toxic steroid lactones or substituted tryptamines of which some may or may not be toxic. They occur in the parotoid glands, skin, and poison of many toads ( genus ''Bufo'') and other amphibians, and in some plants and ...

in secretions of other toads, as well as plants and mushrooms.

Chemistry

Bufagin and bufagins are bufadienolide derivatives. This means they are steroids with a

pyran In chemistry, pyran, or oxine, is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom and containing two double bonds. The molecular formula is C5H6O. There are two isomers of pyran that differ ...

- (delta-)

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

ring attached to ring D (the five-membered one). The difference to digitalis compounds is that the latter have a furan- (gamma-)lactone ring that has one carbon atom and one double bond less.

Effects of bufagins

Some bufagins have effects similar to poisoning by

, having effects on the

cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

, causing

ventricular fibrillation Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and n ...

. Some also have local anesthetic action. The analgesic effects have also been proven, by acting as

Na+/K+-ATPase NA, N.A., Na, nA or n/a may refer to: Chemistry and physics * Sodium, symbol Na, a chemical element * Avogadro constant (''N''A) * Nucleophilic addition, a type of reaction in organic chemistry * Numerical aperture, a number that characterizes a ...

inhibitors on the binding sites of the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. The anti-cancer properties in

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

and melanoma cells, and the

inhibition Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of the proliferation of prostate cancer cells, have also been investigated in cellular models. Some of the bufagin toxins are used in low doses in

traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of acti ...

for similar applications as digoxin is used for in Western medicine (i.e. treatment of heart conditions such as atrial fibrillation). There are at least 86 identified bufadienolides. Examples of bufagins are: * Arenobufagin, from the Argentine toad (''Chaunus arenarum'', synonym ''Bufo arenarum''); * Cinobufagin, from the Chusan Island toad (''Bufo gargarizans''); * Gamabufagin, from the Japanese toad (''Bufo japonicus''); * Marinobufagin, from '' Bufo rubescens'' and the

cane toad The cane toad (''Rhinella marina''), also known as the giant neotropical toad or marine toad, is a large, terrestrial true toad native to South and mainland Central America, but which has been introduced to various islands throughout Oceania ...

(''Bufo marinus''); * Quercicobufagin, from the oak toad (''Anaxyrus quercicus'', synonym ''Bufo quercicus''); * Regularobufagin, from the square-marked toad (''Amietophrynus regularis'', synonym ''Bufo regularis''); * Vallicepobufagin, from the Gulf Coast toad (''Incilius valliceps'', synonym ''Bufo valliceps''); * Viridibufagin, from the

European green toad The European green toad (''Bufotes viridis'') is a species of toad found in steppes, mountainous areas, semi-deserts, urban areas and other habitats in mainland Europe, ranging from far eastern France and Denmark to the Balkans and Western Russi ...

(''Bufo viridis'') These bufagins, and especially cinobufagin, have given rise to a large number of derivatives evaluated as potential anti-tumor drugs.

References

{{Toxins Antiarrhythmic agents Bufanolides