Abstract
A rapid, semiautomated microdilution method was developed to measure the antitrypanosomal activity of large numbers of compounds against blood form Trypanosoma rhodesiense at 37 C in vitro. Parasites harvested from infected rats were incubated for 3 hr in microtitration plates with serial dilutions of test compounds. Inhibition of uptake of radiolabeled thymidine and l-leucine by the parasites served as indicators of antitrypanosomal activity. Repeated measurements of the activity of ethidium bromide demonstrated the sensitivity and precision of the method. Several additional antitrypanosomal drugs were tested in vitro and all except tryparsamide (a pentavalent arsenical) and suramin (a complex polyanion) were consistent with in vivo activity. Antimicrobial agents which are not effective antitrypanosomal drugs failed to show activity in vitro. Other compounds active in vitro included allopurinol and a number of aromatic diamidines, carbamodithioic acid derivatives, and 2-acetylpyridine thiosemicarbazones. This in vitro microtest system was developed as a primary screen for the selection of active compounds in a new Antitrypanosomal Drug Development Program.
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