Molecular Pharmacology, Vol 20, 218-223, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Antimalarial Activity of Selected Aromatic Chelators

II. Substituted Quinolines and Quinoline-N-oxides

¹ Laboratory of Parasitology, The Rockefeller University, New York, New York 10021

The human malaria parasite, Plasmodium falciparum, has been shown in vitro to be sensitive to lipophilic chelators with high metal-binding constants. Growth inhibition of the parasite correlates directly with the ability of the compound to chelate, and favorable activity has been demonstrated among the alkyl thiocarbamates, pyridine-N-oxides and quinolines. The 5-substituted 8-hydroxyquinolines and 2-mercaptoquinoline-N-oxide, which have had some use in medicine and cosmetics, possess these characteristics. They also exhibit active antimalarial effects in vitro at concentrations as low as 5 x 10^-8 M, making them more potent than quinine sulfate in the same system. Antimalarial effects are not antagonized by cobalt or potentiated by iron, but toxicity of the 5-substituted oxines to the parasite is increased by increasing oxygen levels in vitro.

Note:
ACKNOWLEDGMENTS The authors wish to thank Dr. Ernest Bueding and Dr. John Seed for evaluating the mutagenicity of these compounds and Dr. W. Trager for his continued support. The authors also wish to think Drs. E. Bueding and A. Albert for suggestions made during the preparation of the manuscript, and Dr. D. H. Steinberg, Dr. Pierre Huve, and the Sigma-Tau Company for the generous donation of drugs.