| Questions And Answer | Back Directory | [Inhibitor of Nucleic Acid Synthesis]
Sulfonamides act in the pathway of folic acid synthesis and thus act indirectly on DNA synthesis, since the reduced form of folic acid, tetrahydrofolic acid, serves as an essential co-factor in the synthesis of thymidylic acid.
Sulfonamides are analogs of p-aminobenzoic acid. They competitively inhibit dihydropteroate synthetase, the enzyme that condenses p-aminobenzoic acid with dihydropteroic acid in the early stages of folic acid synthesis. Most bacteria need to synthesize folic acid and cannot use exogenous sources of the vitamin. Mammalian cells, in contrast, require preformed folate and this is the basis of the selective action of sulfonamides. The antileprotic sulfone dapsone, and the antituberculosis drug p-aminosalicylic acid, act in a similar way; the basis for their restricted spectrum may reside in differences of affinity for variant forms of dihydropteroate synthetase in the bacteria against which they act.
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