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A dihydropteroate synthetase inhibitor is a drug that inhibits the action of dihydropteroate synthetase. Most are sulfonamides.

Tetrahydrofolate synthesis pathway

In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. DHPS catalyses the conversion of PABA (para-aminobenzoate) to dihydropteroate, a key step in folate synthesis. Folate is necessary for the cell to synthesize nucleic acids (nucleic acids are essential building blocks of DNA and RNA), and in its absence cells will be unable to divide. Hence the sulfonamide antibacterials exhibit a bacteriostatic rather than bactericidal effect.


Folate is not synthesized in mammalian cells, but is instead a dietary requirement. This explains the selective toxicity to bacterial cells of these drugs. These antibiotics are used to treat pneumocystis jiroveci pneumonia, urinary tract infections, and shigellosis.

Two examples are dapsone and sulfamethoxazole.[1]

Another example is the antimalarial sulfadoxine.[2]




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