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The American Journal of Tropical Medicine and Hygiene
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In Vitro Antimalarial Activity of Tetrahydrofolate Dehydrogenase Inhibitors

David G. SixsmithClinical Research Centre, Kenya Medical Research Institute, Pharmacy Department, University of Nairobi, U.S. Army Medical Research Unit—Kenya, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 20778, Nairobi, Kenya

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William M. WatkinsClinical Research Centre, Kenya Medical Research Institute, Pharmacy Department, University of Nairobi, U.S. Army Medical Research Unit—Kenya, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 20778, Nairobi, Kenya

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Jeffrey D. ChulayClinical Research Centre, Kenya Medical Research Institute, Pharmacy Department, University of Nairobi, U.S. Army Medical Research Unit—Kenya, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 20778, Nairobi, Kenya

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Harrison C. SpencerClinical Research Centre, Kenya Medical Research Institute, Pharmacy Department, University of Nairobi, U.S. Army Medical Research Unit—Kenya, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 20778, Nairobi, Kenya

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DOI:
https://doi.org/10.4269/ajtmh.1984.33.772
Volume/Issue:
Volume 33: Issue 5
Page(s):
772–776
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Three tetrahydrofolate dehydrogenase (dihydrofolate reductase = EC 1.5.1.3) inhibitors were tested for antimalarial activity against Plasmodium falciparum, using an in vitro radioisotopic technique. Activity of each drug was tested in both normal RPMI medium 1640 and in modified medium (containing no p-aminobenzoic acid and 2.27 × 10-8 M folic acid) after a 24- or 48-hour exposure. Activity was increased 20- to 85-fold using the modified medium and the longer exposure time. Under all conditions, pyrimethamine and cycloguanil were of equal or greater potency than an experimental pyrimethamine analogue, M&B 35769, against pyrimethamine-sensitive strains, but M&B 35769 was more active than either pyrimethamine or cycloguanil against pyrimethamine-resistant strains.

Author Notes

Present address: Department of Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307.

Copyright:
Copyright © 1984 by The American Society of Tropical Medicine and Hygiene 1984
Accepted:
20 Mar 1984
|
Published Online:
Sep 1984
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