Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs.
The Michaelis-Menten inhibitory constants (Kis) and the concentrations required for 50% inhibition of the Plasmodium falciparum dihydropteroate synthetase were determined for six sulfa drugs. These drugs inhibited the in vitro growth of P. falciparum (50% lethal concentration) at concentrations of 30 to 500 nM; these concentrations were 100 to 1,000 times lower than the concentrations required for 50% inhibition and Kis (6 to 500 microM). The uptake of p-aminobenzoic acid was not inhibited by the sulfa drugs. However, infected erythrocytes took up more labeled sulfamethoxazole than did uninfected erythrocytes. Thus, the concentration of sulfa drugs by malaria parasites may explain how sulfa drugs inhibit in vitro growth of parasites through the inhibition of dihydropteroate synthetase.
Zhang
Y
Y
Department of Microbiology, City University of New York Medical School, New York 10031.
Meshnick
S R
SR
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000818:Animals; D003622:Dapsone / Q000494:pharmacology; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000254:growth & development; D013449:Sulfonamides / Q000494:pharmacology*
D013449:Sulfonamides; D003622:Dapsone; D004094:Dihydropteroate Synthase; D010129:4-Aminobenzoic Acid