Prontosil
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Prontosil, the first commercially available antibacterial with a relatively broad effect (against Gram-positive cocci but not against enterobacteria), was developed by a research team at the Bayer Laboratories of the I.G. Farben conglomerate in Germany. The discovery and development of this first sulfonamide drug opened a new era in medicine.
Sulfonamidochrysoidine (KI-730), first synthesized by Bayer chemists Josef Klarer and Fritz Mietzsch, was tested and found effective against some important bacterial infections in mice by Gerhard Domagk, who subsequently received the 1939 Nobel Prize in Medicine.  Prontosil was the result of five years of research and testing involving thousands of compounds related to azo dyes.
The crucial test result (in a murine model of Streptococcus pyogenes systemic infection) that preliminarily established the antibacterial efficacy of prontosil in mice dates from late December 1931. The readily water-soluble sodium salt of sulfonamidochrysoidine, which gives a burgundy red solution and was trademarked Prontosil, was clinically investigated between 1932 and 1934, first at the nearby hospital at Wuppertal-Elberfeld headed by Philipp Klee, and then at the Dusseldorf university hospital. The results were published in a series of articles in the February 15, 1935 issue of Germany's then pre-eminent medical scientific journal, Deutsche Medizinische Wochenschrift, and were initially received with some scepticism by a medical community bent on vaccination and crude immunotherapy.
As impressive clinical successes with Prontosil started to be reported from all over Europe, and especially after the widely published treatment of Franklin Delano Roosevelt, Jr. (a son of U.S. president Franklin D. Roosevelt), acceptance was quick and dozens of medicinal chemistry teams set out to improve on Prontosil. Jacques and Therese Trefouel and their team at the French Pasteur Institute found in 1936 that Prontosil is metabolized to sulfanilimide (para-aminophenylsulfonamide), a much simpler, colorless molecule, redefining Prontosil as a prodrug.
Sulfanilamide was already off patent (it had first been synthesized by Paul Gelmo, a chemistry student working at the University of Vienna in his 1909 thesis who however had not realized its medical potential) and cheap to produce. The sulfanilamide moiety was also easy to link into other molecules, and soon gave rise to hundreds of second-generation sulfonamide drugs. As a result, Prontosil failed to make the profits in the marketplace hoped for by Bayer. Although quickly eclipsed by these newer "sulfa drugs" and, in the mid-1940s and through the 1950s, penicillin and a string of newer antibiotics that proved more effective against more types of bacteria, Prontosil remained on the market until the 1960s. Prontosil's discovery ushered in the era of antibiotics and had a profound impact on pharmaceutical research, drug laws, and medical history.
Sulfonamide-trimethoprim combinations are used extensively for opportunistic infections in patients with AIDS, urinary infections and burn therapy. However their uses are greatly replaced by beta-lactam antibiotics.
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