Prontosil rubrum

Domagk also observed that prontosil rubrum was ineffective against bacteria in test tube studies. This was an unusual finding. In current practice, activity at the... 

Figure 1.1. Opposite) Sulpha drugs and their mode of action. The first sulpha drug to be used medically was the red dye prontosil rubrum (a). In the early 1930s, experiments illustrated that the administration of this dye to mice infected with haemolytic streptococci prevented the death of the mice. This drug, while effective in vivo, was devoid of in vitro antibacterial activity. It was first used clinically in 1935 under the name Streptozon. It was subsequently shown that prontosil rubrum was enzymatically reduced by the liver, forming sulphanilamide, the actual active antimicrobial agent (b). Sulphanilamide induces its effect by acting as an anti-metabolite with respect to /iflra-aminobenzoic acid (PABA) (c). PABA is an essential component of tetrahydrofolic acid (THF) (d). THF serves as an essential co-factor for several cellular enzymes. Sulphanilamide (at sufficiently high concentrations) inhibits manufacture of THF by competing with PABA. This effectively inhibits essential THF-dependent enzyme reactions within the cell. Unlike humans, who can derive folates from their diets, most bacteria must synthesize it de novo, as they cannot absorb it intact from their surroundings...

Sulfamidochrysoidine (Prontosil Rubrum, 1.20), a red dye, was marketed as an antibiotic in the 1930s by the German company I.G. Farbenindustrie, now part of Bayer. Based on his work on the project, Gerhard Domagk was awarded the Nobel Prize in Medicine in 1939 (Figure 1.9).1... 

Dyes have a long history of use in medicine both for diagnostic and therapeutic purposes. Thus, crystal violet (76) is used for staining bacteria (Gram test), and the azo dye Prontosil rubrum (77) was the first drug that produced the active agent sulfanilamide (78) on reduction in the body [67],... 

Figure 2.4 Sulfamidochrysoidine 10 (Prontosil rubrum , Bayer) and related antibacterial sulfonamides act via the metabolite sulfanilamide 11, which is an antimetabolite of p-aminobenzoic acid in the bacterial biosynthesis of dihydrofolic acid.

A classic success case of the brute-force approach is the discovery of Prontosil rubrum , the first sulfonamide type... 

Figure 1.12. Stractures of the sulfonamide drag prontosil rubrum , its antibacterially active metabolite sulfanilamide, and the bacterial metabolite p-Aminobenzoic acid. Sulfanilamide acts as an antimetabolite (i.e., competitive inhibitor) in the synthesis of folic acid, of which aminobenzoic acid is a component...

Fig. 10.18 A, Some sulphonamides B,prontosil rubrum C, unsubstituted diaminobenzylpyrimidines D, trimethoprim E, tetroxoprim F, dapsone.

Sulfonamide drugs are bacteriostatic synthetic compounds, the first chemotherapeutics used in human medicine. The progenitor of the class was a red azo dye, 2,4-diaminoben-zene -sulfonamide, called prontosil rubrum. The sulfonamides include sulfanilamide (4-amino-benzenesulfonamide) and numerous compounds related to it (Fig. 10). 

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