Skip to Main Content

++

SULFONAMIDES

++

The sulfonamide drugs were the first effective chemotherapeutic agents to be employed systemically for the prevention and cure of bacterial infections in humans. The considerable medical and public health importance of their discovery and their subsequent widespread use was quickly reflected in the sharp decline in morbidity and mortality figures for treatable infectious diseases. The advent of penicillin and subsequently of other antibiotics has diminished the usefulness of the sulfonamides, and they presently occupy a relatively small place in the therapeutic armamentarium of the physician. However, the introduction in the mid-1970s of the combination of trimethoprim and sulfamethoxazole has increased the use of sulfonamides for the prophylaxis and treatment of specific microbial infections.

+

History. Investigations in 1932 at the I. G. Farbenindustrie resulted in the patenting of prontosil and several other azo dyes containing a sulfonamide group. Prompted by the knowledge that synthetic azo dyes had been studied for their action against streptococci, Domagk tested the new compounds and observed that mice with streptococcal and other infections could be protected by prontosil. In 1933, Foerster reported giving prontosil to a 10-month-old infant with staphylococcal septicemia and achieving a dramatic cure. Favorable clinical results with prontosil and its active metabolite, sulfanilamide, in puerperal sepsis and meningococcal infections awakened the medical profession to the new field of antibacterial chemotherapy, and experimental and clinical articles soon appeared in profusion. The development of the carbonic anhydrase inhibitor–type diuretics and the sulfonylurea hypoglycemic agents followed from observations made with the sulfonamide antibiotics. For discovering the chemotherapeutic value of prontosil, Domagk was awarded the Nobel Prize in Medicine for 1938 (Lesch, 2007).

Chemistry. The term sulfonamide is employed herein as a generic name for derivatives of para-aminobenzenesulfonamide (sulfanilamide); the structural formulas of selected members of this class are shown in Figure 52–1. Most of them are relatively insoluble in water, but their sodium salts are readily soluble. The minimal structural prerequisites for antibacterial action are all embodied in sulfanilamide itself. The SO2NH2 group is not essential as such, but the important feature is that the sulfur is linked directly to the benzene ring. The para-NH2 group (the N of which has been designated as N4) is essential and can be replaced only by moieties that can be converted in vivo to a free amino group. Substitutions made in the amide NH2 group (position N1) have variable effects on antibacterial activity of the molecule. However, substitution of heterocyclic aromatic nuclei at N1 yields highly potent compounds.

++
Figure 52–1.

Structural formulas of selected sulfonamides and para-aminobenzoic acid. The N of the para-NH2 group is designated as N4; that of the amide NH2, as N1.

Graphic Jump Location
++

Effects on Microbes

++

Sulfonamides have a wide range of antimicrobial activity against both gram-positive and ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.