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Am. J. Trop. Med. Hyg., 28(5), 1979, pp. 781-792
Copyright © 1979 by The American Society of Tropical Medicine and Hygiene

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Studies on the 2,4-Diamino-6-Substituted Quinazolines

I. Antimalarial Activities of 2,4-Diamino-6-[(3,4-Dichlorobenzyl)-Nitrosoamino]-Quinazoline (CI-679) as Exhibited in Rhesus Monkeys Infected with the Ro or Ro/PM Strains of Plasmodium cynomolgi*

L. H. Schmidt{dagger} AND Richard N. Rossan{ddagger}
National Center for Primate Biology, University of California, Davis, California 95616, and Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35205

This report summarizes the results of appraisals of various activities of CI-679 (a 2,4-diamino-6-amino-substituted quinazoline) in rhesus monkeys infected with the Ro and Ro/PM strains of Plasmodium cynomolgi. In subjects inoculated with sporozoites, CI-679, administered in appropriate schedules in doses up to and including the maximum tolerated level, neither prevented development of infections with these strains nor cured those already established. Although these evaluations showed that CI-679 was devoid of activity against both early and late tissue schizonts, they indicated that this compound had significant blood schizonticidal activity and suggested that such activity was much greater in infections with the Ro strain than in those with the Ro/PM strain. This latter suggestion, contrary to results of earlier experiments in mice infected with Plasmodium berghei, led to studies of the activities of CI-679 in trophozoite-induced infections. These showed that the total course dose of CI-679 required for cure of previously untreated infections with the Ro/PM strain was tenfold that required for cure of comparable infections with the Ro strain. They also showed that infections with either strain, treated previously with subcurative doses, were often not cured by doses of CI-679 that eradicated previously untreated infections regularly. Subsequent studies showed that emergence of parasites resistant to CI-679 was responsible for these retreatment failures and that this resistance was retained through mosquito transfer.

Accepted for publication March 10, 1979.


* The experimental components of this report were supported by Research Grants AI-05888 and FR-00169 from the National Institutes of Health and a special assistance grant from Parke Davis and Company, Research Laboratories, Ann Arbor, Michigan, to the University of California, Davis. Manuscript preparation was supported in part by Contract DADA 17-69-C-9104 between the U.S. Army Medical Research and Development Command and Southern Research Institute and in part by the latter Institute. This is contribution number 1531 from the Army Research Program on Malaria.

Address reprint requests to: L. H. Schmidt, Kettering-Meyer Laboratory, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205.


{dagger} Present address: Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35205.


{ddagger} Present address: Gorgas Memorial Laboratory, P. O. Box 2016, Balboa Heights, Canal Zone.






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Copyright © 1979 by the American Society of Tropical Medicine and Hygiene.