1921
Volume 38, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Pyronaridine, a 9-substituted 1-aza-acridine, was assayed for in vitro activity against clinical and field isolates as well as characterized clones of . The in vitro antimalarial activity of pyronaridine was compared to activities of standard antimalarials against multidrug-resistant isolates of from eastern and northern Thailand using an assay based on the inhibition of schizont maturation. Isolates from eastern Thailand (n = 30) were susceptible to pyronaridine (IC 8.40 nM), mefloquine (IC 6.97 nM), and amodiaquine (IC 12.7 nM) and resistant to chloroquine (IC 361 nM), quinine (IC 388 nM), and pyrimethamine (IC 11,800 nM). The isolates from northern Thailand (n = 7) showed no statistical difference in susceptibility to pyronaridine (IC 10.1 nM), amodiaquine (IC 7.29 nM), and mefloquine (IC 5.48 nM); however, isolates were significantly more susceptible to chloroquine (IC 167 nM), quinine (IC 248 nM), and pyrimethamine (IC 1,980 nM). These data suggest a lack of cross-resistance between pyronaridine and either chloroquine, quinine, or pyrimethamine. Using the same assay system the in vitro activity of pyronaridine was evaluated against isolates from treatment failures of mefloquine or enpiroline from eastern Thailand. The IC values for mefloquine against five recrudescent isolates were significantly higher (IC 16.4 nM) than the field isolates collected from the same region (IC 6.97 nM); however, there was no significant difference in the pyronaridine susceptibility between the isolates from the field study (IC 8.89 nM) and the isolates from the treatment failures (IC 8.40 nM). These observations suggest a lack of cross-resistance to mefloquine following treatment failure with either mefloquine or enpiroline. Using an in vitro assay based on the measurement of the inhibition of nucleic acid synthesis the high levels of antimalarial activity of pyronaridine was further evidenced by the comparatively low IC values of the drugs against two reference clones, D-6 African (IC 4.73 nM) and the W-2 Indochina (IC 15.4 nM).

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/content/journals/10.4269/ajtmh.1988.38.24
1988-01-01
2017-09-21
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http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.1988.38.24
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  • Accepted : 06 Jul 1987

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