Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.
Article Details
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Hong YL, Hossler PA, Calhoun DH, Meshnick SR
Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.
Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63.
- PubMed ID
- 7486915 [ View in PubMed]
- Abstract
Forty-four sulfa drugs were screened against crude preparations of recombinant Pneumocystis carinii dihydropteroate synthetase. The apparent Michaelis-Menten constants (Km) for p-aminobenzoic acid and 7,8-dihydro-6-hydroxymethylpterin pyrophosphate were 0.34 +/- 0.02 and 2.50 +/- 0.71 microM, respectively. Several sulfa drugs, including sulfathiazole, sulfachlorpyridazine, sulfamethoxypyridazine, and sulfathiourea, inhibited dihydropteroate synthetase approximately as well as sulfamethoxazole, as determined by the concentrations which cause 50% inhibition and/or by Ki. For all sulfones and sulfonamides tested, unsubstituted p-amino groups were necessary for activity, and sulfonamides containing an N1-heterocyclic substituent were found to be the most effective inhibitors. Folate biosynthesis in isolated intact P. carinii was approximately equally sensitive to inhibition by sulfamethoxazole, sulfachlorpyridazine, sulfamethoxypyridazine, sulfisoxazole, and sulfathiazole. Two of these drugs, sulfamethoxypyridazine and sulfisoxazole, are known to be less toxic than sulfamethoxazole and should be further evaluated for the treatment of P. carinii pneumonia.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Acetyl sulfisoxazole Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails Sulfamerazine Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails Sulfamethazine Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails Sulfaphenazole Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails Sulfisoxazole Dihydropteroate synthase Protein Escherichia coli (strain K12) YesInhibitorDetails