Relations Among Antimalarial Drugs: Results of Studies with Cycloguanil-, Sulfone-, or Chloroquine-Resistant Plasmodium Berghei in Mice

Abstract

Summary Three lines of Plasmodium berghei were made highly resistant to cycloguanil hydrochloride, 4,4′-diaminodiphenylsulfone (DDS), or chloroquine diphosphate by the repeated treatment of infected mice with partially suppressive doses. They were then maintained on constant doses of the drugs to favor a fixed degree of resistance. Collectively, the three lines were resistant to the major types of suppressive antimalarial drugs. Fourteen drugs were tested systematically for suppressive effects against these lines in parallel with the parent strain. The response of the lines to various heterologous drugs ranged from strong cross-resistance to hypersensitivity. The composite results indicated the following grouping of the drugs: I: cycloguanil hydrochloride, chlorguanide, and pyrimethamine; II: DDS and sulfadiazine; III: chloroquine, amodiaquine, amopyroquine, acridine N-oxide CI-423, quinacrine, naphthalene BW 377-C54, and quinine; IV: primaquine; and V: oxophenarsine. The data suggest possible alternative drugs for dealing with various types of resistant strains. They also may serve in drug development as a basis for recognizing compounds with new modes of action.