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Sulfonamides or Sulfa Drugs as Antimetabolites:
The sulfonamides are synthetic antimicrobial agents with a
wide spectrum encompassing most gram-positive and many gram-negative
organisms. These drugs were the first efficient treatment to
be employed systematically for the prevention and cure of bacterial
infections.
Their use introduced and substantiated the concept of metabolic
antagonism. Sulfonamides, as antimetabolites, compete with para-aminobenzoic
acid (PABA) for incorporation into folic acid. The action of
sulfonamides illustrates the principle of selective toxicity
where some difference between mammal cells and bacterial cells
is exploited. All cells require folic acid for growth. Folic
acid (as a vitamin is in food) diffuses or is transported into
human cells. However, folic acid cannot cross bacterial cell
walls by diffusion or active transport. For this reason bacteria
must synthesize folic acid from p-aminobenzoic acid.
Sulfonamides or sulfa drugs have the following general structures
as shown in the graphic on the left.
Sulfanilamide which was the first compound used of this type
has H's at R1 and R4. To date about 15,000 sulfonamide derivatives,
analogues, and related compounds have been synthesized.
This has lead to the discovery of many useful drugs which
are effective for diuretics, antimalerial and leprosy agents,
and antithyroid agents. The basic structure of sulfonamide cannot
be modified if it is to be an effective competitive "mimic"
for p-aminobenzoic acid. Essential structural features are the
benzene ring with two substituents para to each other; an amino
group in the fourth position; and the singly substituted 1-sulfonamido
group.
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