Sulfanilamide molecular structure

FIGURE 7.33 Molecular structures of some antibiotics (a) sulfanilamide (b) penicillin G and (c) tetracycline. 

The mode of action of sulfanilamides became known around 1947, when the structure and biosynthesis of folic acid were elucidated. This compound is built by bacteria from the heterocyclic pteroyl moiety, p-aminobenzoate, and glutamate. p-Aminobenzene-sulfonamide (9.89, sulfanilamide) is a competitive inhibitor of the synthase enzyme, acting as an antimetabolite of p-aminobenzoate. Occasionally, the sulfanilamide can even be incorporated into the modified folate, resulting in an inactive compound and thus an inactive enzyme. This theory, proposed by Woods and Fildes in 1940, became the first molecular explanation of drug action. 

A time span of 33 years has elapsed since the original formulation of the antimetabolite theory by Fildes1 based upon the discovery by Woods2 of the biological antagonism between sulfanilamide (1 b) and p-aminobenzoic acid (la), two compounds strikingly similar to each other in chemical structure and molecular dimensions (see illustration). Up to the present day, this theory... 

The AAP approach, with some variations, has recently been applied with varying degrees of success to the prediction of several other structures including, in order of increasing molecular complexity, high pressure solid phases of benzene [73], the three polymorphs of sulfanilamide [74], and the low and high temperature phases of poly(p-hydroxybenzoic acid) [75]. 

Figure 20.4 The structural similarity of p-aminobenzoic acid and a sulfanilamide. (Reprinted with permission of John Wiley and Sons, Inc. from Korolkovas, Essentials of Molecular Pharmacology, Copyright 1970.)...

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