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.
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Departamento de Ultra-estrutura e Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
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D000818:Animals; D000880:Anthraquinones; D001312:Aurintricarboxylic Acid / Q000031:analogs & derivatives; D001559:Benzhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004396:Coloring Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005840:Gentian Violet / Q000494:pharmacology; D006416:Hematoxylin / Q000494:pharmacology; D037102:Lectins / Q000494:pharmacology; D009284:Naphthols / Q000138:chemical synthesis / Q000494:pharmacology; D010635:Phenolphthaleins / Q000138:chemical synthesis / Q000494:pharmacology; D010851:Picrates / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013331:Strychnine / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000880:Anthraquinones; D001559:Benzhydryl Compounds; D004396:Coloring Agents; D037102:Lectins; D009284:Naphthols; D010635:Phenolphthaleins; D010851:Picrates; D014344:Trypanocidal Agents; C011454:dipicrylamine; D001312:Aurintricarboxylic Acid; C017037:aurin; D013331:Strychnine; D005840:Gentian Violet; C511975:purpurin anthraquinone; D006416:Hematoxylin