Screening of drugs for rapid activity against Trypanosoma cruzi trypomastigotes in vitro.
Previous studies to find drugs with an existing product licence which were active at 4 degrees C within 24 hours and which would be suitable to prevent the transmission of Chagas' disease during blood transfusion were unsuccessful. As part of an alternative approach to identify drugs active at 37 degrees C or 25 degrees C within 2 hours, over 280 compounds were screened against bloodstream trypomastigotes of Trypanosoma cruzi Sonya strain in a microslide test in vitro. Although compounds from a wide range of chemical groups were tested only three polyene antibiotics showed outstanding trypanocidal activity. Amphotericin B, candicidin and trichomycin lysed all trypomastigotes at 8 X 10(-6) as determined by microscopical techniques. However, these compounds also showed toxicity to mammalian erythrocytes at the same concentration after a 24 hours incubation period. It seems unlikely that this approach will yield a candidate replacement for gentian violet.
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001769:Blood / Q000469:parasitology; D002174:Candicidin / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000187:drug effects; D005840:Gentian Violet / Q000494:pharmacology; D006801:Humans; D007814:Larva; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009930:Organic Chemicals; D013696:Temperature; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000935:Antifungal Agents; D009930:Organic Chemicals; D014344:Trypanocidal Agents; D002174:Candicidin; C100192:hachimycin; D000666:Amphotericin B; D005840:Gentian Violet