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Am. J. Trop. Med. Hyg., 32(2), 1983, pp. 231-257
Copyright © 1983 by The American Society of Tropical Medicine and Hygiene

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Appraisals of Compounds of Diverse Chemical Classes for Capacities to Cure Infections with Sporozoites of Plasmodium Cynomolgi*,{dagger}

L. H. Schmidt{ddagger}
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama, and the Department of Pharmacology, The Medical Center, University of Alabama in Birmingham, Birmingham, Alabama

Compounds (265) of widely diverse structures were appraised for radical curative activity in rhesus monkeys infected with sporozoites of the B strain of Plasmodium cynomolgi, using an evaluation system that provided a preliminary assessment with from 0.1–1.0 g of compound and tests against one to five active infections. None of 32 compounds in a miscellaneous structure category, none of seven agents of antibiotic origin, none of 12 1,5-naphthyridines, and none of seven 7-aminoquinolines exhibited curative activity at the largest test doses. There was a suggestion that one of 12 newly synthesized pyrocatechols was curative. Two of 20 6-aminoquinolines effected cure at or near maximum tolerated doses. In contrast, 90 of 174 newly synthesized 8-aminoquinolines effected cure; 18 of the 90 being as active as primaquine, eight twice as active, and six four times as active. There were major disagreements between the above results and those recorded by others in mice inoculated with sporozoites of P. berghei yoelii or P. yoelii nigeriensis. These discrepancies were of serious dimensions in evaluations of the 8-aminoquinolines. This, plus previous near flawless performances of P. cynomolgi in identifying agents that would cure naturally acquired P. vivax infections, led to the suggestion that the abbreviated simian model employed in these studies be used hereafter in primary screening of new agents for radical curative activity.

Accepted for publication August 13, 1982.


* The experimental studies recorded in this report were supported by Contract DADA 17-69-C-9104 between the U.S. Army Medical Research and Development Command and Southern Research Institute, Birmingham, AL, and Research Grant M2/118/119 from the World Health Organization to the Southern Research Institute. Manuscript preparation has been supported by Contract DAMD 17-80-C-0080 between the U.S. Army Medical Research and Development Command and the Board of Trustess of University of Alabama. This is contribution 1646 from the U.S. Army Research Program on Antiparasitic Drugs.


{dagger} Address reprint requests to: L. H. Schmidt, Department of Pharmacology, The Medical Center, University of Alabama in Birmingham, Box 191, University Station, Birmingham, Alabama 35294.


{ddagger} Present address: Department of Pharmacology, The Medical Center, University of Alabama in Birmingham, Birmingham, Alabama 35294.






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Copyright © 1983 by the American Society of Tropical Medicine and Hygiene.