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Appraisals of Compounds of Diverse Chemical Classes for Capacities to Cure Infections with Sporozoites of Plasmodium Cynomolgi
L. H. Schmidt
L. H. Schmidt
Kettering-Meyer Laboratory, Southern Research Institute, Department of Pharmacology, The Medical Center, University of Alabama in Birmingham, Birmingham, Alabama
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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.
Author Notes
Present address: Department of Pharmacology, The Medical Center, University of Alabama in Birmingham, Birmingham, Alabama 35294.
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