American Society for Microbiology, Antimicrobial Agents and Chemotherapy, 8(51), p. 2842-2847, 2007
DOI: 10.1128/aac.00288-07
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ABSTRACT We have recently reported that the attachment of a bulky metabolically stable tert -butyl group at the C-2 position of a quinoline ring in primaquine results in a tremendous improvement in the blood schizontocidal antimalarial activity of 8-quinolinamine. Because free heme released from hemoglobin catabolism in a malarial parasite is highly toxic, the parasite protects itself mainly by crystallization of heme into insoluble nontoxic hemozoin. We now demonstrate the ability of 2- tert -butylprimaquine to inhibit in vitro beta-hematin formation, to form a complex with heme with a stoichiometry of 1:1, and to enhance heme-induced hemolysis. The results described herein indicate that a major improvement in the blood-schizontocidal antimalarial activity of 2- tert -butylprimaquine might be due to a disturbance of heme catabolism pathway in the malarial parasite.