Bufagin

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Bufagin
Identifiers
Properties
C24H34O5
Molar mass 402.531 g·mol−1
Density 1.240 g/cm3 [1]
Melting point 212-213 ˚C [2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Bufagin is a toxic steroid C24H34O5 [3] obtained from toad's milk, the poisonous secretion of a skin gland on the back of the neck of a large toad ( Rhinella marina , synonym Bufo marinus, the cane toad). The toad produces this secretion when it is injured, scared or provoked. Bufagin resembles chemical substances from digitalis in physiological activity and chemical structure.

Contents

Bufagin also refers to any of several similar substances found as components of the mixture bufotoxin in secretions of other toads, as well as plants and mushrooms.

History

The discovery of bufagin has taken place in the fall of 1910, where John Jacob Abel and David I. Macht are investigating the property of unknown substances from a tropical toad, Bufo agua. [4] They collected the "milky secretion" squirted out of toad’s parotid gland due to the control of the central nervous system while it was strongly irritated. They observed the semifluid substance is quickly dried in the air and formed a yellow and hard scales that shared a similar appearance with dried snake venom. After the experiments with the poison, John Jacob Abel and David I. Macht found there are epinephrin and a newly discovered substance exist within the secretion, which they originally gave the name of “bufagin” to this digitalis-like substance. They also quantitatively analyzed the amounts of epinephrin and bufagin in the venom, which showed that 0.734 gram of bufagin with respect to 0.1 gram of epinephrin presented.

Chemistry

Gamabufagin Gamabufagin.png
Gamabufagin

Bufagin and bufagins are bufadienolide derivatives. This means they are steroids with a six-membered lactone (α-pyrone) ring attached to ring D (the five-membered one). The difference to digitalis compounds is that the latter have a fix-membered lactone (α-furan) ring that has one carbon atom and one double bond less.

Bufagin is the category name of a large bufadienolide family, there are at least 86 identified bufagins. [5] Examples of bufagins are:

These bufagins, and especially cinobufagin, have given rise to a large number of derivatives evaluated as potential anti-tumor drugs. [6]

Synthesis

Transformation of bufotalin to cinobufagin Bufotalin to cinobufagin.png
Transformation of bufotalin to cinobufagin

Two structurally similar bufagins can be utilized to develop a synthetic method, which is the transformation of bufotalin to cinobufagin. [7] Cinobufagin is known for its potential as the precursor of many anti-tumor drugs and bufotalin is an important venom found within the cane toad. This synthesis method involves 6 steps.

Effects of bufagins

Some bufagins have effects similar to poisoning by digitalis, having effects on the cardiac muscle, causing ventricular fibrillation. Some also have local anesthetic action. The analgesic effects have also been proven, [8] by acting as Na+/K+-ATPase inhibitors on the binding sites of the cell membrane. The anti-cancer properties in leukemia and melanoma cells, and the inhibition of the proliferation of prostate cancer cells, have also been investigated in cellular models. [9] [10] [11] Some of the bufagin toxins are used in low doses in traditional Chinese medicine for similar applications as digoxin is used for in Western medicine (i.e. treatment of heart conditions such as atrial fibrillation). [12]

These bufagins, and especially cinobufagin, have given rise to a large number of derivatives evaluated as potential anti-tumor drugs.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Cane toad</span> Worlds largest true toad

The cane toad, 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 and the Caribbean, as well as Northern Australia. It is a member of the genus Rhinella, which includes many true toad species found throughout Central and South America, but it was formerly assigned to the genus Bufo.

<span class="mw-page-title-main">Cardiac glycoside</span> Class of organic compounds

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses are as treatments for congestive heart failure and cardiac arrhythmias; however, their relative toxicity prevents them from being widely used. Most commonly found as secondary metabolites in several plants such as foxglove plants, these compounds nevertheless have a diverse range of biochemical effects regarding cardiac cell function and have also been suggested for use in cancer treatment.

<span class="mw-page-title-main">5-MeO-DMT</span> Chemical compound

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the Colorado River toad. Like its close relatives DMT and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include Five-methoxy, the power, bufo, and toad venom.

<span class="mw-page-title-main">Common toad</span> Species of amphibian

The common toad, European toad, or in Anglophone parts of Europe, simply the toad, is a frog found throughout most of Europe, in the western part of North Asia, and in a small portion of Northwest Africa. It is one of a group of closely related animals that are descended from a common ancestral line of toads and which form a species complex. The toad is an inconspicuous animal as it usually lies hidden during the day. It becomes active at dusk and spends the night hunting for the invertebrates on which it feeds. It moves with a slow, ungainly walk or short jumps, and has greyish-brown skin covered with wart-like lumps.

<span class="mw-page-title-main">Bufotenin</span> Psychedelic drug found in toads, mushrooms and plants

Bufotenin is a tryptamine derivative, more specifically, a DMT analog, related to the neurotransmitter serotonin. It is an alkaloid found in some species of mushrooms, plants and toads, especially the skin.

<span class="mw-page-title-main">Bufotoxin</span> Class of chemical compounds

Bufotoxins are a family of toxic steroid lactones or substituted tryptamines of which some are toxic. They occur in the parotoid glands, skin, and poison of many toads and other amphibians, and in some plants and mushrooms. The exact composition varies greatly with the specific source of the toxin. It can contain 5-MeO-DMT, bufagins, bufalin, bufotalin, bufotenin, bufothionine, dehydrobufotenine, epinephrine, norepinephrine, and serotonin. Some authors have also used the term bufotoxin to describe the conjugate of a bufagin with suberylarginine.

<span class="mw-page-title-main">Bufotalin</span> Chemical compound

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.

<span class="mw-page-title-main">Colorado River toad</span> Species of amphibian

The Colorado River toad, also known as the Sonoran Desert toad, is a toad species found in northwestern Mexico and the southwestern United States. It is well known for its ability to exude toxins from glands within its skin that have psychoactive properties.

<span class="mw-page-title-main">True toad</span> Family of amphibians

A true toad is any member of the family Bufonidae, in the order Anura. This is the only family of anurans in which all members are known as toads, although some may be called frogs. The bufonids now comprise more than 35 genera, Bufo being the best known.

<i>Rhinella icterica</i> Species of amphibian

Rhinella icterica is a species of toad in the family Bufonidae that is found in northeastern Argentina, southern Brazil, and eastern Paraguay. "Cururu" is its indigenous name and refers to the male advertisement call that is a melodious tremolo. "Cururu toad", without the specifier "yellow", is a common name used for a few other closely related species.

<span class="mw-page-title-main">Marinobufagenin</span> Chemical compound

Marinobufagenin (marinobufagin) is a cardiotonic bufadienolide steroid. It can be found in the plasma and urine of human subjects with myocardial infarction, kidney failure, and heart failure. It is also secreted by the toad Bufo rubescens and other related species such as Bufo marinus. It is a vasoconstrictor with effects similar to digitalis.

<span class="mw-page-title-main">Arenobufagin</span> Chemical compound

Arenobufagin is a cardiotoxic bufanolide steroid secreted by the Argentine toad Bufo arenarum. It has effects similar to digitalis, blocking the Na+/K+ pump in heart tissue.

<span class="mw-page-title-main">Cinobufagin</span> Chemical compound

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.

The cane toad in Australia is regarded as an exemplary case of an invasive species. Australia's relative isolation prior to European colonisation and the industrial revolution, both of which dramatically increased traffic and import of novel species, allowed development of a complex, interdepending system of ecology, but one which provided no natural predators for many of the species subsequently introduced. The recent, sudden inundation of foreign species has led to severe breakdowns in Australian ecology, after overwhelming proliferation of a number of introduced species, for which the continent has no efficient natural predators or parasites, and which displace native species; in some cases, these species are physically destructive to habitat, as well. Cane toads have been very successful as an invasive species, having become established in more than 15 countries within the past 150 years. In the Environment Protection and Biodiversity Conservation Act 1999, the Australian government listed the impacts of the cane toad as a "key threatening process".

<span class="mw-page-title-main">Bufanolide</span> Chemical compound

Bufanolide is a C24 steroid and, indirectly, a parent structure of bufadienolide. Its derivatives was found in Bufo and Scilla, as an aglycone of cardiac glycosides and is usually toxic.

<span class="mw-page-title-main">Bufothionine</span> Chemical compound

Bufothionine is a sulfur-containing compound which is present in the bufotoxins secreted by the parotoid gland of certain toads of the genera Bufo and Chaunus. This specific compound can be found in the skin of certain species of toad such as the Asiatic Toad, Chaunus arunco, Chaunus crucifer, Chaunus spinulosus, and Chaunus arenarum.

HuaChanSu is a traditional Chinese medicine extracted from the skin of toads from the genus Bufo that is believed by some to slow the spread of cancerous cells. The parotoid gland of toads of the Bufo genus secrete a venom, which is dried and dissolved in water. This solution, HuaChanSu, is injected into a cancerous area and targets specific cancer cells. HuaChanSu is undergoing further trials, and its effect is not completely understood.

<span class="mw-page-title-main">Bufalin</span> Chemical compound

Bufalin is a cardiotonic steroid toxin originally isolated from Chinese toad venom, which is a component of some traditional Chinese medicines.

Native to both South and Central America, Cane toads were introduced to Australia in the 1930s and have since become an invasive species and a threat to the continent's native predators and scavengers.

<i>Protoopalina hylarum</i> Species of single-celled organism

Protoopalina hylarum is a species of protozoa in the Opalinidae family, and an amphibian parasite. It was first described in 1911 by Janet W. Raff as Opalina hylarum.

References

  1. Crowfoot, Dorothy (1935). "X-ray crystallography of the toad poisons bufagin and cinobufagin and of strophanthidin". Chemistry & Industry (London, United Kingdom): 568-9.
  2. Jensen, H.; Evans, E.A. (February 1934). "Chemical Studies on Toad Poisons". Journal of Biological Chemistry. 104 (2): 307–316. doi: 10.1016/S0021-9258(18)75767-0 .
  3. ChemicalBook: bufagin
  4. Abel, John J.; Macht, David I. (27 May 1911). "THE POISONS OF THE TROPICAL TOAD, BUFO AGUA: A PRELIMINARY COMMUNICATION". Journal of the American Medical Association. LVI (21): 1531. doi:10.1001/jama.1911.02560210003002.
  5. S. Steyn, Pieter; R. van Heerden, Fanie (1998). "Bufadienolides of plant and animal origin". Natural Product Reports. 15 (4): 397–413. doi:10.1039/A815397Y. PMID   9736996. S2CID   30031690.
  6. Gao, Huimin; Popescu, Ruxandra; Kopp, Brigitte; Wang, Zhimin (2011). "Bufadienolides and their antitumor activity". Natural Product Reports. 28 (5): 953–969. doi:10.1039/C0NP00032A. PMID   21416078.
  7. Pettit, George R.; Kamano, Yoshiaki (December 1972). "Steroids and related natural products. 78. Bufadienolides. 21. Synthesis of cinobufagin from bufotalin". The Journal of Organic Chemistry. 37 (25): 4040–4044. doi:10.1021/jo00798a015. PMID   4643019.
  8. Wang, G.; G. Sun; et al. (1994). "The application of traditional Chinese medicine to the management of hepatic cancerous pain". J Tradit Chin Med. 14 (2): 132–138. PMID   7967697.
  9. Jiun-Yih Yeh; William J. Huang; Shu-Fen Kan; Paulus S. Wang (2002). "Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells". The Prostate. 54 (2): 112–124. doi:10.1002/pros.10172. PMID   12497584. S2CID   36322137.
  10. Jing, Y.; H. Ohizumi; et al. (1994). "Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells". Jpn J Cancer Res. 85 (6): 645–651. doi:10.1111/j.1349-7006.1994.tb02408.x. PMC   5919529 . PMID   8063619.
  11. Yin, P. H.; Liu, X; Qiu, Y. Y.; Cai, J. F.; Qin, J. M.; Zhu, H. R.; Li, Q (2012). "Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers: New hope for cancer patients". Asian Pacific Journal of Cancer Prevention. 13 (11): 5339–43. doi: 10.7314/apjcp.2012.13.11.5339 . PMID   23317181.
  12. Bick, RJ; Poindexter, BJ; Sweney, RR; Dasgupta, A (2002). "Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: Cardiotoxicity due to more than Na, K-ATPase blocking". Life Sciences. 72 (6): 699–709. doi:10.1016/s0024-3205(02)02302-0. PMID   12467910.