8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization

Jonathan L. Vennerstrom, Edwin O. Nuzum, Robert E. Miller, Arnulf Dorn, Lucia Gerena, Prasad A. Dande, William Y. Ellis, Robert G. Ridley, Wilbur K. Milhous

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Abstract

From the Walter Reed Army Institute of Research (WRAIR) inventory, thirteen 8-aminoquinoline analogs of primaquine were selected for screening against a panel of seven Plasmodium falciparum clones and isolates. Six of the 13 8-aminoquinolines had average 50% inhibitory concentrations between 50 and 100 nM against these P. falciparum clones and were thus an order of magnitude more potent than primaquine. However, excluding chloroquine- resistant clones and isolates, these 8-aminoquinolines were all an order of magnitude less potent than chloroquine. None of the 8-aminoquinolines was cross resistant with either chloroquine or mefloquine. In contrast to the inactive primaquine prototype, 8 of the 13 8-aminoquinolines inhibited hematin polymerization more efficiently than did chloroquine. Although alkoxy or aryloxy substituents at position 5 uniquely endowed these 13 8- aminoquinolines with impressive schizontocidal activity, the structural specificity of inhibition of both parasite growth and hematin polymerization was low.

Original languageEnglish (US)
Pages (from-to)598-602
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume43
Issue number3
StatePublished - Mar 1999

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Vennerstrom, J. L., Nuzum, E. O., Miller, R. E., Dorn, A., Gerena, L., Dande, P. A., Ellis, W. Y., Ridley, R. G., & Milhous, W. K. (1999). 8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization. Antimicrobial Agents and Chemotherapy, 43(3), 598-602.