Screening of natural and synthetic drugs against Trypanosoma cruzi. 1. Establishing a structure/activity relationship.

The activity of 45 compounds against bloodstream forms of Trypanosoma cruzi was investigated. The aim was to consider new agents which might subsequently be assayed for chemoprophylaxis in donated blood. In a preliminary screening the drugs were assayed (50 to 1,000 microM at 29 degrees C) and those active against bloodstream forms at concentrations below 600 microM were selected for further assays under blood-bank conditions (4 degrees C/24 h). Three compounds isolated from natural sources and six synthetic agents were selected. The active compounds of plant origin included purpurin, a member of the trihydroxylated anthraquinone group, which is known to exhibit trypanocidal activity. Among the active synthetic compounds, five displayed a common structural feature in that they were potentially one-electron acceptors, via reductive functional groups. All five compounds form tricentered C or N intermediates, joined in a hypothetical 'Y' radical pattern. It is possible that the trypanocidal mechanisms initiated by these compounds are similar to those found with crystal violet, since this dye, which is already used in endemic areas for the treatment of banked blood, also conforms to this general Y structural pattern.

A Ga-68-labeled tetrabromophthalein (Ga-68 BP-IDA) for positron imaging of hepatobiliary function: concise communication.

We describe the chemical synthesis of an iminodiacetic-acid-substituted tetrabromo-o-cresolphthalein (BP-IDA), which complexes Ga-68 tightly. The liver uptake, bile excretion, and urinary excretion of the complex were examined in rats. Maximum liver uptake reached 60%, and 1-hr cumulative bile excretion was 75% of injected dose. Urinary excretion in rats with ligated common bile duct remained below 1%. Competitive action of exogenous bilirubin on hepatobiliary excretion of the Ga complex was less pronounced than that of bromosulfophthalein. The absolute activity determination of the positron emitter Ga-68, the high accumulation in the liver, the low urinary excretion, and the weak competition from exogenous bilirubin are promising features of this radiopharmaceutical for the quantitative study of hepatobiliary function.