In vitro activity of bisquinoline WR268,668 against African clones and isolates of Plasmodium falciparum

L. K. Basco, S. L. Andersen, W. K. Milhous, J. Le Bras, J. L. Vennerstrom

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Abstract

The in vitro activity of a new bisquinoline, WR268,668, was determined against chloroquine-susceptible and chloroquine-resistant African clones and isolates of Plasmodium falciparum using an isotopic semimicro drug susceptibility assay. The chloroquine-resistant clone (mean 50% inhibitory concentration [IC50] = 61.2 nM) was 11 times less susceptible to WR268,668 than the chloroquine-susceptible clone (IC50 = 5.75 nM). A similar result was obtained with fresh clinical isolates, with the chloroquine-susceptible isolates (IC50 = 5.36 nM, n = 11) being significantly (P < 0.05) more susceptible to WR268,668 than the chloroquine-resistant isolates (IC50 = 16.1 nM, n = 18). The compound WR268,668 exhibited a high activity against some moderately chloroquine-resistant isolates. There was a significant positive correlation between the in vitro responses to chloroquine and WR268,668 (r = 0.904, P < 0.05). Combinations of WR268,668 and desipramine, a chloroquine efflux inhibitor, showed that resistance to WR268,668 can be reversed against the chloroquine-resistant clone and that desipramine has no effect on the activity of WR268,668 against the chloroquine-susceptible clone. The results of the study indicate the presence of cross-resistance between chloroquine and WR268,668, and suggest that the basis of resistance to WR268,668 may be similar to that of other 4-aminoquinolines.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume50
Issue number2
DOIs
StatePublished - Jan 1 1994

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Chloroquine
Plasmodium falciparum
Clone Cells
Inhibitory Concentration 50
Desipramine
In Vitro Techniques

ASJC Scopus subject areas

  • Parasitology
  • Virology
  • Infectious Diseases

Cite this

In vitro activity of bisquinoline WR268,668 against African clones and isolates of Plasmodium falciparum. / Basco, L. K.; Andersen, S. L.; Milhous, W. K.; Le Bras, J.; Vennerstrom, J. L.

In: American Journal of Tropical Medicine and Hygiene, Vol. 50, No. 2, 01.01.1994, p. 200-205.

Research output: Contribution to journalArticle

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abstract = "The in vitro activity of a new bisquinoline, WR268,668, was determined against chloroquine-susceptible and chloroquine-resistant African clones and isolates of Plasmodium falciparum using an isotopic semimicro drug susceptibility assay. The chloroquine-resistant clone (mean 50{\%} inhibitory concentration [IC50] = 61.2 nM) was 11 times less susceptible to WR268,668 than the chloroquine-susceptible clone (IC50 = 5.75 nM). A similar result was obtained with fresh clinical isolates, with the chloroquine-susceptible isolates (IC50 = 5.36 nM, n = 11) being significantly (P < 0.05) more susceptible to WR268,668 than the chloroquine-resistant isolates (IC50 = 16.1 nM, n = 18). The compound WR268,668 exhibited a high activity against some moderately chloroquine-resistant isolates. There was a significant positive correlation between the in vitro responses to chloroquine and WR268,668 (r = 0.904, P < 0.05). Combinations of WR268,668 and desipramine, a chloroquine efflux inhibitor, showed that resistance to WR268,668 can be reversed against the chloroquine-resistant clone and that desipramine has no effect on the activity of WR268,668 against the chloroquine-susceptible clone. The results of the study indicate the presence of cross-resistance between chloroquine and WR268,668, and suggest that the basis of resistance to WR268,668 may be similar to that of other 4-aminoquinolines.",
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