Sulfonamide is one of a group of antibiotics commonly referred to as Sulfa drugs which were discovered in the 1930’s. Exactly in 1935, Gerhard Domagk , a medical doctor employed by a German dye manufacturer made a breakthrough discovery by finding that a red dye, 4′-sulfamyl-2,4- diaminoazo-benzene, which was later named prontosil. It was active against streptococcal infection in vivo, but not in vitro. (Bendjeddou, et al. 2016). He made the discovery in a desperate, but successful attempt to save his daughter who was dying of a streptococci infection. Gerhard Domagk had demonstrated that the dye prontosil functioned as antibiotic when injected into infected mice but not when tested against bacteria growing in a test tube. The reason for this unusual behavior was understood later. (Bhattacharjee, 2016). Domagk’s discovery led to an extremely productive period of discovery in antibiotics. He was awarded the Nobel Prize for medicine in 1939. In 1936, a year after Domagk’s discovery of the anti-streptococcus activity of the dye prontosil, Ernest Fourneau of the Pasteur Institute in Paris discovered that prontosil breaks down in the human body to produce sulfanilamide (Scheme 1), which is the active agent that kills streptococcus bacteria. Fourneau’s discovery triggered a flurry of research on structural derivatives of sulfanilamide which resulted in development of a family of highly successful antibiotics that have saved millions of lives. (Nicolaou, et al.2017).
Domagk’s discovery quickly resulted in the development of a variety of sulfonamides, all of which were essentially substituted sulfanilamides. Since then there have been many analogues of sulfanilamide developed as pharmacological agents that display a wide range of biological activities. For example, Glibenclamide has found use as a hypoglycaemic agent, E7070 as an anticancer agent, Amprenavir is used in HIV therapy, Furosemide as a diuretic, Acetazolamide as a carbonic anhydrase inhibitor, and Sulfathiazole as an antibacterial agent.
Sulfapyridine was shown to be effective against pneumonia in 1938. Sulfacetamide found highly successful use in fighting urinary tract infections starting in 1941. Succinoylsulfathiazole has been used against gastrointestinal tract infections since 1942. Sulfathiazole was used very effectively during World War II to fight infection in soldiers with battle wounds. Sulfanilamide itself, a potent antibiotic, never gained widespread use due to its greater human toxicity versus its various derivatives. (Supuran, et al.2004).