1921
Volume 32, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Experimental studies were undertaken in tissue culture and mice infected with a cloned derivative of , Y strain to determine the efficacy of two 2-substituted 5-nitroimidazole compounds, MK-436 and L634,549. The use of an X-irradiated myoblast culture system proved better than a conventional fibroblast culture for assaying the activity of compounds against intracellular parasite stages. MK-436 showed activity against amastigotes at a level of 25 µg/ml and L634,549 a dihydroxy metabolite of MK-436 showed activity 2 µg/ml. Neither compound caused morphological damage to the host cells at levels tested (250 µg/ml). By contrast, nifurtimox, which was active at 2 µg/ml, caused significant host cell damage at 100 µg/ml. In mice, studies in the chronic infection showed that MK-436 was curative at a level of 30 mg/kg if given daily for 20 days. Neither nifurtimox nor benznidazole were fully curative when given at a level of 100 mg/kg daily for 20 days. These studies showed that administration of MK-436 with a suitable solvent, PEG 400, enhanced its efficacy fourfold, and that efficacy was also enhanced by increasing the treatment interval. Since MK-436 showed better efficacy in chronic rodent infections than either nifurtimox or benznidazole, such compounds should be evaluated for efficacy in human Chagas' disease.

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/content/journals/10.4269/ajtmh.1983.32.1242
1983-11-01
2017-09-23
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http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.1983.32.1242
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  • Accepted : 27 May 1983

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