1921
Volume 28, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Four 6-thio-, one 6-sulfinyl-, and two 6-sulfonyl-substituted 2,4-diaminoquin-azolines were evaluated for capacities to cure established infections with the chloroquine-resistant Vietnam Oak Knoll and pyrimethamine-resistant Malayan Camp-CH/Q strains of in owl monkeys. As compared with the doses of standard drugs required for cure of infections with drug-susceptible strains or doses of the newly developed aminoalcohols required for cure of either drug-susceptible or drug-resistant strains, each of these quinazolines effected cure of infections with the Oak Knoll strain at a remarkably small daily dose. However, doses required for cure of infections with the Camp-CH/Q strain were from 4–48 times those required for cure of infections with the Oak Knoll strain, suggesting that the activities of these quinazolines, like those of 6-amino-substituted derivatives, were compromised by pyrimethamine resistance. This suggestion received support from expanded studies involving WR-158,122 and WR-159,412, the most active of the agents examined, and the multidrug-resistant Vietnam Smith strain of and Vietnam Palo Alto strain of , as well as the Oak Knoll and Camp-CH/Q strains. These studies also showed that significant fractions of infections with the Oak Knoll, Camp-CH/Q, and Palo Alto strains treated previously with subcurative doses of the above derivatives failed to respond to doses that regularly cured previously untreated infections. These treatment failures proved to be due to emergence of parasites resistant to the quinazolines.

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/content/journals/10.4269/ajtmh.1979.28.793
1979-09-01
2017-11-23
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http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.1979.28.793
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  • Accepted : 10 Mar 1979

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