Prontosil , production

Possibly the most significant discovery in the metabolism of aromatic azo compounds had implications that heralded the age of modem chemotherapy. It was shown that the bactericidal effect of the azo dye Prontosil in vivo was in fact due to the action of its transformation product, sulfanilamide, which is an antagonist of 4-aminobenzoate that is required for the synthesis of the vitamin folic acid. Indeed, this reduction is the typical reaction involved in the first stage of the biodegradation of aromatic azo compounds. 

The bmte force approach to dmg discovery is still widely used, and one of the reasons why dmg design is now largely done by major pharmaceutical companies. In fact, prontosil was discovered at the biggest pharmaceutical company of the era, the German IG Farben , which was dismantled after the war for its involvement with the production of poisons used in the holocaust. 

In this scheme, a foreign compound, A, may foUow one of four main routes of metabolism to produce the product, C. In the first route i), A, an inactive compound, could be converted into an active compound, 5, by a Phase I reaction (oxidation, reduction, or hydrolysis). Examples of this type of reaction are hydroxylation of acetanahde, reduction of Prontosil, or hydrolysis of cyclophosphamide. The Compound, B, may be further metabolized by a Phase II... 

Prontosil, p-[(2,4-diaminophenyl)azo]benzenesulfonamide, was first synthesized in Germany in 1932 as a product of azo-dye research at 1. G. Far-benindustrie. It was soon tested for chemotherapeutic activity, because it bound very strongly to protein fibers. In 1933, it became the first drug to effectively cure blood stream infections. The early investigations of the biological activity of Prontosil required direct testing on animal infections, since the drug appeared to be inactive in vitro. 

---