Sulfanilamide (also spelled sulphanilamide) is a

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactiv ...

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 ...

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. Th ...

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 start ...

derivatized Derivatization is a technique used in chemistry which converts a chemical compound into a product (the reaction's derivate) of similar chemical structure, called a derivative. Generally, a specific functional group of the compound participates i ...

with a

group. Powdered sulfanilamide was used by the Allies in

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 World War II by country, vast majority of the world's countries—including all of the great power ...

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 subs ...

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 ...

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 class ...

preparations, primarily for treatment of vaginal yeast infections mainly vulvovaginitis 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 usua ...

''. 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 res ...

s. Examples include: * Furosemide, 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 or ...

* 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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

Sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Listeria monocytogenes' ...

, 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. 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 a ...

, 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 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 include substituted purin ...

s and pyrimidines. Mammals 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 DN ...

s, methionine, and

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − for ...

. 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 of

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 P ...

, who directed the testing of the prodrug Prontosil in 1935, and

Jacques Tréfouël Jacques Tréfouël (9 November 1897, Le Raincy – 11 July 1977, Paris) was a French medical chemist. He collaborated closely with his wife, Thérèse Tréfouël, including on the discovery of sulfanilamide. Biography From 1920 to 1928 he ...

and Thérèse Tréfouël, who along with Federico Nitti and Daniel Bovet 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, a medicine consisting of sulfanilamide dissolved in diethylene glycol poisoned and killed more than 100 people as a result of acute kidney failure, prompting new US regulations for drug testing. In 1938, the Food, Drug and Cosmetic Act 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. Mathematicall ...

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 An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would ...

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 solub ...

: 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 miscible wi ...

. It is practically insoluble in

chloroform Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various re ...

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 b ...

, 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 ato ...

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 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 hy ...

l cream or suppository (through the vaginal mucosa). It is metabolized by acetylation like other

s and excreted through the urine.

External links

References

{{Sulfonamides and trimethoprim Sulfonamide antibiotics