Sulfanilamide (also spelled sulphanilamide) is a sulfonamide

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

drug. Chemically, it is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

consisting of an

aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...

derivatized with a sulfonamide group. Powdered sulfanilamide was used by the

Allies An alliance is a relationship among people, groups, or states that have joined together for mutual benefit or to achieve some common purpose, whether or not explicit agreement has been worked out among them. Members of an alliance are called ...

World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...

to reduce infection rates and contributed to a dramatic reduction in mortality rates compared to previous wars. Sulfanilamide is rarely if ever used systemically due to

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

and because more effective sulfonamides are available for this purpose. Modern

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

have supplanted sulfanilamide on the battlefield; however, sulfanilamide remains in use today in the form of

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

preparations, primarily for treatment of

vaginal yeast infection Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burn ...

s mainly

vulvovaginitis Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy. The three ma ...

which is caused by ''

Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...

''. The term "sulfanilamides" is also sometimes used to describe a family of molecules containing these

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...

s. Examples include: *

Furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by m ...

, a

loop diuretic Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure ...

* Sulfadiazine, an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

* Sulfamethoxazole, an

Mechanism of action

As a sulfonamide antibiotic, sulfanilamide functions by competitively inhibiting (that is, by acting as a substrate analogue) enzymatic reactions involving ''para''-aminobenzoic acid (PABA). Specifically, it competitively inhibits the enzyme

dihydropteroate synthase Dihydropteroate synthase is an enzyme classified under . It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans. This makes it a useful target for sulfonamide antibiotics, which compete with the PA ...

. PABA is needed in enzymatic reactions that produce

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

, which acts as a

coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...

in the synthesis of

purine Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...

s and pyrimidines.

Mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s do not synthesize their own folic acid so are unaffected by PABA inhibitors, which selectively kill bacteria. However, this effect can be reversed by adding the end products of one-carbon transfer reactions, such as

thymidine Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. ...

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

, and serine. PABA can also reverse the effects of sulfonamides.

History

Sulfanilamide was first prepared in 1908 by the Austrian chemist Paul Josef Jakob Gelmo (1879–1961) as part of his dissertation for a doctoral degree from the

Technische Hochschule A ''Technische Hochschule'' (, plural: ''Technische Hochschulen'', abbreviated ''TH'') is a type of university focusing on engineering sciences in Germany. Previously, it also existed in Austria, Switzerland, the Netherlands (), and Finland (, ). ...

Vienna en, Viennese , iso_code = AT-9 , registration_plate = W , postal_code_type = Postal code , postal_code = , timezone = CET , utc_offset = +1 , timezone_DST ...

. It was patented in 1909.

Gerhard Domagk Gerhard Johannes Paul Domagk (; 30 October 1895 – 24 April 1964) was a German pathologist and bacteriologist. He is credited with the discovery of sulfonamidochrysoidine (KL730) as an antibiotic for which he received the 1939 Nobel Prize in Phy ...

, who directed the testing of the prodrug

Prontosil Prontosil is an antibacterial drug of the sulfonamide group. It has a relatively broad effect against gram-positive cocci but not against enterobacteria. One of the earliest antimicrobial drugs, it was widely used in the mid-20th century but is ...

in 1935, and Jacques Tréfouël and

Thérèse Tréfouël Thérèse Tréfouël (née Boyer, 19 June 1892 — 9 November 1978) was a French chemist. Along with her husband, Jacques Tréfouël, she is best known for her research on sulfamides, a novel class of antibiotic drugs. Education and personal l ...

, who along with Federico Nitti and

Daniel Bovet Daniel Bovet (23 March 1907 – 8 April 1992) was a Swiss-born Italian pharmacologist who won the 1957 Nobel Prize in Physiology or Medicine for his discovery of drugs that block the actions of specific neurotransmitters. He is best known for hi ...

in the laboratory of

Ernest Fourneau Ernest Fourneau (4 October 1872 – 5 August 1949) was a French pharmacist graduated in Pharmacy 1898 for the Paris university specialist in medicinal chemical and pharmacology who played a major role in the discovery of synthetic local anesthetic ...

at the

Pasteur Institute The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines f ...

, determined sulfanilamide as the active form, are generally credited with the discovery of sulfanilamide as a chemotherapeutic agent. Domagk was awarded the Nobel Prize for his work. In 1937,

Elixir sulfanilamide Elixir sulfanilamide was an improperly prepared sulfonamide antibiotic that caused mass poisoning in the United States in 1937. It is believed to have killed more than 100 people. The public outcry caused by this incident and other similar disast ...

, a medicine consisting of sulfanilamide dissolved in

diethylene glycol Diethylene glycol (DEG) is an organic compound with the formula (HOCH2CH2)2O. It is a colorless, practically odorless, and hygroscopic liquid with a sweetish taste. It is a four carbon dimer of ethylene glycol. It is miscible in water, alcohol, ...

poisoned and killed more than 100 people as a result of acute

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, prompting new US regulations for drug testing. In 1938, the

Food, Drug and Cosmetic Act The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a set of laws passed by the United States Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of f ...

was passed. It was only the solvent and not the sulfanilamide that was the problem, as sulfanilamide was widely and safely used at the time in both tablet and powder form.

Chemical and physical properties

Sulfanilamide is a yellowish-white or white crystal or fine powder. It has a

density Density (volumetric mass density or specific mass) is the substance's mass per unit of volume. The symbol most often used for density is ''ρ'' (the lower case Greek letter rho), although the Latin letter ''D'' can also be used. Mathematical ...

of 1.08 g/cm³ and a

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends ...

of 164.5-166.5 °C. The pH of a 0.5% aqueous solution of Sulfanilamide is 5.8 to 6.1. It has a λ_max of 255 and 312 nm.

Solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubil ...

: One gram of sulphanilamide dissolves in approximately 37 ml alcohol or in 5 ml

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

. It is practically insoluble in

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

, or

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...

Contraindications

Sulphanilamide is contraindicated in those known to be hypersensitive to sulfonamides, in nursing mothers, during pregnancy near term and in infants less than 2 months of age.

Adverse effects

Since sulfanilamide is used almost exclusively in topical vaginal preparations these days, adverse effects are typically limited to

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

or local skin reactions. If absorbed, systemic side effects commonly seen with sulfanilamides may occur.

Pharmacokinetics

A small amount of sulfanilamide is absorbed following topical application or when administered as a

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...

l cream or

suppository A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal ...

(through the vaginal mucosa). It is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

by acetylation like other sulfonamides and excreted through the urine.

External links

References

{{Sulfonamides and trimethoprim Sulfonamide antibiotics