Sulfa drugs, antibacterial

Sulfa Drugs Antibacterials Discovered in the Nick of Time... 

Isothiazole substituents have been attached to /3-lactam antibiotics and to macrocyclic antibiotics such as erythromycin. The sulfa drug, Sulfasomizole (244) also has good antibacterial activity. Thiosemicarbazones of 5-formyl- and 5-acetylisothiazoles show high activity against the pox group of viruses (65AHC(4)107). 

Control of tuberculosis, long one of the scourges of mankind, began with the introduction of effective antibacterial agents. Thus, this disease was treated initially with some small measure of success with various sulfa drugs the advent of the antibiotic, streptomycin, provided a major advance in antitubercular therapy, as did the subsequent discovery of isoniazid and its analogs. 

Sulfa drugs were the first important antibacterials... 

Now we come to the question what is the basis of the antibacterial action of the sulfa drugs Many useful drugs in human medicine are enzyme inhibitors, small molecules that frequently bear a structural resemblance to the substrates or products of enzyme-catalyzed reactions. So it is with the sulfonamides. 

The discovery of a novel structural class of antibacterials is notable, as these are few and far between. The sulfa drugs, p-lactams, quinohnes, tetracyclines, macrohdes, and aminoglycosides have been around for decades. Multiple improvements have been made over time in each of these classes but without breaking out into new structural classes. There are two notable, recent examples of new stractural classes of antibacterials and these are worth knowing about. 

Sulfa drugs were the first important antibacterials. Sulfa drugs act by inhibiting bacterial folic acid synthesis. 

Sulfanilamide was the first of a range of synthetic antibacterial drugs known collectively as sulfa drugs. These agents are antibacterial because they mimic in size, shape, and polarity the carboxylic acid p-aminobenzoic acid. 

Mammals must obtain their tetrahydrofolate requirements from their diet, but microorganisms are able to synthesize this material. This offers scope for selective action and led to the use of sulfanilamide and other antibacterial sulfa drugs, compounds that competitively inhibit the biosynthetic enzyme (dihydropteroate synthase) that incorporates p-aminobenzoic acid into the structure (see Box 7.23). 

The nitrofurans and sulfa drugs are antibacterial feed additives that... 

Before the 1930s bacterial diseases were a major cause of death. Pneumonia and tuberculosis were major killers. Since the advent of the sulfa drugs and penicillins many bacterial diseases have been controlled. The antibacterial drugs will be discussed by type. We will see that some of these are antibiotics, an antibacterial substance produced by a living organism such as a bacterium or fungus, rather than synthesized in the laboratory. 

The arsenal of antibacterials available for the treatment of infectious diseases has expanded exponentially since then. Currently, as illustrated in Fig. 1, the repertoire includes the (J-lactams (e.g. 3) sulfa drugs (e.g. 4) macrolides (e.g. 5, erythromycin A), nitrofuran drugs (e.g. 6, furazolidone), and many aminoglycosides. 

Would formulating a sulfa drug with PABA be likely to increase or decrease its antibacterial properties ... 

Gerhard Domagk Physiology/Medicine Prontosil, first antibacterial sulfa drug... 

Ehrlich s approach to developing arsphenamine involved extensive screening studies on each newly prepared compound. Information gained from earlier screens helped determine the structure of the next compound to be synthesized. This iterative method is the predominant method for modem lead optimization in medicinal chemistry. Under his method, Ehrlich s antibacterial research continued to progress and ultimately resulted in the discovery of the sulfa drugs. 

As expected, the reaction of a sulfonyl chloride with ammonia produces a sulfonamide. This reaction is used in the preparation of sulfanilamide, a sulfa drug that was one of the first antibacterial agents ... 

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