In Vitro Activity of Bisquinoline WR268,668 Against African Clones and Isolates of Plasmodium falciparum
| Autor: | S. L. Andersen, L. K. Basco, J. Le Bras, Jonathan L. Vennerstrom, W. K. Milhous |
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| Rok vydání: | 1994 |
| Předmět: |
Plasmodium falciparum
Drug Resistance Clone (cell biology) Antimalarials Chloroquine Virology medicine Animals Humans Drug Interactions Malaria Falciparum IC50 Cross-resistance Cyclohexylamines Molecular Structure biology Desipramine Biological activity biology.organism_classification Molecular biology In vitro Infectious Diseases Africa Quinolines Parasitology Efflux medicine.drug |
| Zdroj: | The American Journal of Tropical Medicine and Hygiene. 50:200-205 |
| ISSN: | 1476-1645 0002-9637 |
| DOI: | 10.4269/ajtmh.1994.50.200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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