Brucine, is an
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
closely related to
strychnine
Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the eye ...
, most commonly found in the ''
Strychnos nux-vomica
''Strychnos nux-vomica'', the strychnine tree, also known as nux vomica, poison fruit, semen strychnos, and quaker buttons, is a deciduous tree native to India and to southeast Asia. It is a medium-sized tree in the family Loganiaceae that grow ...
'' tree. Brucine poisoning is rare, since it is usually ingested with strychnine, and strychnine is more toxic than brucine. In synthetic chemistry, it can be used as a tool for
stereospecific chemical syntheses.
Brucine is named from the genus ''
Brucea
''Brucea'' is a genus of plant in the family Simaroubaceae. It is named for the Scottish scholar and explorer James Bruce
James Bruce of Kinnaird (14 December 1730 – 27 April 1794) was a Scottish traveller and travel writer who confirmed ...
'', named after
James Bruce
James Bruce of Kinnaird (14 December 1730 – 27 April 1794) was a Scottish traveller and travel writer who confirmed the source of the Blue Nile. He spent more than a dozen years in North Africa and Ethiopia and in 1770 became the first Europ ...
who brought back ''Brucea antidysenterica'' from Ethiopia.
History
Brucine was discovered in 1819 by
Pelletier Pelletier is a common surname of French origin. Notable people with this surname include:
*Anne-Marie Pelletier, French Bible scholar
*Anne-Sophie Pelletier, French politician
*Annie Pelletier, Canadian diver
*Benoît Pelletier, Quebec Liberal Par ...
and
Caventou in the bark of the ''Strychnos nux-vomica'' tree. While its structure was not deduced until much later, it was determined that it was closely related to strychnine in 1884, when the chemist Hanssen converted both strychnine and brucine into the same molecule.
Identification
Brucine can be detected and quantified using
liquid chromatography-mass spectrometry
A liquid is a nearly incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of the four fundamental states of matter (the others being solid, gas, an ...
. Historically, brucine was distinguished from strychnine by its reactivity toward chromic acid.
Applications
Chemical applications
Since brucine is a large chiral molecule, it has been used in
chiral resolution
Chiral resolution, or enantiomeric resolution, is a process in stereochemistry for the separation of racemic compounds into their enantiomers. It is an important tool in the production of optically active compounds, including drugs. Another term wi ...
. Fisher first reported its use as a resolving agent in 1899, and it was the first natural product used as an
organocatalyst
In organic chemistry, organocatalysis is a form of catalysis in which the rate of a chemical reaction is increased by an Organic compound, organic catalyst. This "organocatalyst" consists of carbon, hydrogen, sulfur and other nonmetal elements fo ...
in a reaction resulting in an enantiomeric enrichment by
Marckwald, in 1904. Its bromide salt has been used as the stationary phase in
HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
in order to selectively bind one of two anionic enantiomers. Brucine has also been used in
fractional distillation
Fractional distillation is the separation of a mixture into its component parts, or fractions. Chemical compounds are separated by heating them to a temperature at which one or more fractions of the mixture will vaporize. It uses distillation to ...
in acetone in order to resolve dihydroxy
fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
, as well as diarylcarbinols.
Medical applications
While brucine has been shown to have good anti-tumor effects, on both
hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
It occurs in t ...
and breast cancer, its narrow
therapeutic window
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
has limited its use as a treatment for cancer.
Brucine is also used in traditional Chinese medicine as an anti-inflammatory and
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
agent, as well as in some
Ayurveda
Ayurveda () is an alternative medicine system with historical roots in the Indian subcontinent. The theory and practice of Ayurveda is pseudoscientific. Ayurveda is heavily practiced in India and Nepal, where around 80% of the population repo ...
and
homeopathy
Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths, believe that a substance that causes symptoms of a dis ...
drugs.
Alcohol denaturant
Brucine is one of the many chemicals used as a
denaturant to make alcohol unfit for human consumption.
Cultural references
One of the most famous cultural references to brucine occurs in ''
The Count of Monte Cristo
''The Count of Monte Cristo'' (french: Le Comte de Monte-Cristo) is an adventure novel written by French author Alexandre Dumas (''père'') completed in 1844. It is one of the author's more popular works, along with ''The Three Musketeers''. Li ...
'', the novel by French author
Alexandre Dumas
Alexandre Dumas (, ; ; born Dumas Davy de la Pailleterie (), 24 July 1802 – 5 December 1870), also known as Alexandre Dumas père (where '' '' is French for 'father', to distinguish him from his son Alexandre Dumas fils), was a French writer ...
. In a discussion of
mithridatism
Mithridatism is the practice of protecting oneself against a poison by gradually self-administering non-lethal amounts. The word is derived from Mithridates VI, the King of Pontus, who so feared being poisoned that he regularly ingested small dos ...
, Monte Cristo states:
“Well, suppose, then, that this poison was brucine, and you were to take a milligramme the first day, two milligrams the second day, and so on…at the end of a month, when drinking water from the same carafe, you would kill the person who drank with you, without your perceiving…that there was any poisonous substance mingled with this water.”
Brucine in also mentioned in the 1972 version of ''
The Mechanic'', in which the hitman Steve McKenna betrays his mentor, aging hitman Arthur Bishop, using a celebratory glass of wine spiked with brucine, leaving Bishop to die of an apparent heart attack.
Such fictions run contrary to reality in the very properties which make brucine useful as a denaturant, and useless as a covert poison. While being only about one-eighth as toxic as strychnine, its threshold of bitterness occurs at 69% greater dilution. A drink laden with brucine, overwhelmingly bitter at far below lethal concentration, would cause an intended victim to gag on the first sip.
Safety
Brucine intoxication occurs very rarely, since it is usually ingested with strychnine. Symptoms of brucine intoxication include muscle spasms, convulsions,
rhabdomyolysis
Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...
, and
acute kidney injury
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are cla ...
. Brucine’s mechanism of action closely resembles that of
strychnine
Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the eye ...
. It acts as an antagonist at
glycine receptor
The glycine receptor (abbreviated as GlyR or GLR) is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory ...
s and paralyzes inhibitory neurons.
The probable fatal dose of brucine in adults is 1 g.
In other animals, the LD
50 varies considerably.
References
External links
Brucine INCHEM.org
{{Authority control
Quinoline alkaloids
Plant toxins
Bitter compounds
Convulsants
Catechol ethers
Glycine receptor antagonists