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Am. J. Trop. Med. Hyg., 33(5), 1984, pp. 772-776
Copyright © 1984 by The American Society of Tropical Medicine and Hygiene

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In Vitro Antimalarial Activity of Tetrahydrofolate Dehydrogenase Inhibitors*

David G. Sixsmith, William M. Watkins, Jeffrey D. Chulay{dagger} AND Harrison C. Spencer
Clinical Research Centre, Kenya Medical Research Institute, P.O. Box 20778, Nairobi, Kenya, Pharmacy Department, University of Nairobi, P.O. Box 30197, Nairobi, Kenya, U.S. Army Medical Research Unit—Kenya, P.O. Box 401, APO New York 09675, and Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333

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 x 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.

Accepted for publication March 20, 1984.


* Address reprint requests to: Dr. Harrison C. Spencer, Division of Parasitic Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia 30333.


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




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Copyright © 1984 by the American Society of Tropical Medicine and Hygiene.