Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by p-aminobenzoic acid, p-aminobenzoylglutamic acid and folic acid |
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| Authors: | W M Watkins D G Sixsmith J D Chulay H C Spencer |
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| Institution: | 1. Clinical Research Centre, Kenya Medical Research Institute, Nairobi and Wellcome Trust Research Laboratories, P.O. Box 43640, Nairobi, Kenya;2. Clinical Research Centre, Kenya Medical Research Institute, Department of Pharmacy, University of Nairobi, Nairobi, Kenya;3. Clinical Research Centre, Kenya Medical Research Institute, U.S. Army Medical Research Unit - Kenya;4. Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333, U.S.A. |
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| Abstract: | The activity of pyrimethamine and sulfadoxine against two strains of Plasmodium falciparum has been studied in vitro by a radioisotopic technique. Low level antagonism of pyrimethamine resulted from the inclusion of p-aminobenzoic acid, p-aminobenzoylglutamic acid or folic acid in the test medium. Sulfadoxine activity was antagonised slightly by p-aminobenzoic but not by p-aminobenzoylglutamic acid, and antagonised markedly by folic acid at concentrations above 4 X 10(-8) M. At 10(-7) M folic acid, a concentration lower than that of normal RPMI medium 1640, sulfadoxine activity was reduced 7000 to 9000-fold in comparison with controls. These results are of importance in terms of the utilisation of folates by P. falciparum, the susceptibility of the parasite to antifolate drugs and the in vitro determination of parasite susceptibility. |
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| Keywords: | Falciparum malaria Folate utilisation Pyrimethamine Sulfadoxine PABA PABG FA folic acid |
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