Sulfanilamide is a competitive inhibitor for bacterial enzyme dihydropteroate synthetase with IC50 of 320 μM.Target: dihydropteroate synthetase; AntibacterialSulfanilamide containing the sulfonamide functional group displays inhibitory activity for dihydropteroate synthetase partially purified from Escherichia coli which normally uses para-aminobenzoic acid (PABA) for synthesizing the necessary folic acid acting as a coenzyme in the synthesis of purine, pyrimidine and other amino acids, exhibiting an IC 50 of 320 μM for dihydropteroate synthetasea and Km of 2.5 uM for PABA [1]. Sulfanilamide shows IC50 of 286.8 μg/mL for recombinant S. cerevisiae strains with wild-type FOL1 genes, but the single mutation 55Trp to 55Ala or 57Pro to 57Ser within the putative active site of the fungal DHPS confers resistance to Sulfanilamide with IC50 of >800 μg/mL [2]. Administration of Sulfanilamide with the dosage of 100 mg/kg/day is effective in the prevention of P. carinii infection in the immunosuppressed rat model. When the dosage of sulfaguanidine and Sulfanilamide reduced to 10 mg/kg/day, breakthrough P. carinii infection occurs in the rats [3].
References:
[1]. McCullough, J.L. and T.H. Maren, Inhibition of dihydropteroate synthetase from Escherichia coli by sulfones and sulfonamides. Antimicrob Agents Chemother, 1973. 3(6): p. 665-9.
[2]. Meneau, I., et al., Pneumocystis jiroveci dihydropteroate synthase polymorphisms confer resistance to sulfadoxine and sulfanilamide in Saccharomyces cerevisiae. Antimicrob Agents Chemother, 2004. 48(7): p. 2610-6.
[3]. Hughes, W.T. and J. Killmar, Monodrug efficacies of sulfonamides in prophylaxis for Pneumocystis carinii pneumonia. Antimicrob Agents Chemother, 1996. 40(4): p. 962-5.