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Am. J. Trop. Med. Hyg., 65(1), 2001, pp. 19-20
Copyright © 2001 by The American Society of Tropical Medicine and Hygiene

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American Journal of Tropical Medicine and Hygiene, Vol 65, Issue 1, 19-20
Copyright © 2001 by American Society of Tropical Medicine and Hygiene

Research Articles


Short report: floxacrine analog WR 243251 inhibits hematin polymerization

A Dorn, JP Scovill, WY Ellis, H Matile, RG Ridley, and JL Vennerstrom

Floxacrine was a promising antimalarial compound that led to the identification of WR 243251. On the basis of their structures, we suspected that these compounds might be good inhibitors of hematin polymerization. Indeed, WR 243251 was as potent and floxacrine was only 2-fold less potent than chloroquine as inhibitors of this process. However, this hematin polymerization inhibition did not completely account for the increased antimalarial potency of WR 243251 versus chloroquine. The WR 243251 ketone hydrolysis product WR 243246 was without activity against hematin polymerization. These data also confirm that hematin polymerization inhibition can be quite sensitive to small changes in inhibitor structure.


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