Effect of heterocyclic analogues of triphenylmethane dyes against Trypanosoma cruzi.
Several heterocyclic analogues of triphenylmethane dyes have been synthesized. Their in vitro activity has been evaluated using the epimastigote forms of Trypanosoma cruzi as an assay system. The malachite green and gentian violet dyes previously reported as trypanocidal agents were also tested for comparison. Among the compounds tested, the 2-benzothienyl-bis-(4,4'-dimethylaminophenyl) derivative proved to be the most interesting, because of its high selectivity in killing parasites. The ID50, defined as the concentration which produced 50% reduction in (3H) thymidine incorporation in DNA after 18 hours or in viable parasites after five days of incubation with the above compounds, was 0.2 ng ml-1 and less than 1 ng ml-1, respectively. The relative toxicity, measured by its effect on cultured human HeLa cells, was over 10,000-fold higher. By contrast, gentian violet only showed a ten-fold higher inhibitory effect for T. cruzi. The other derivatives synthesized were active in various degrees. According to these results, a structure-activity relationship for these compounds is proposed.
De Diego
C
C
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Avendaño
C
C
Alcina
A
A
Carrasco
L
L
Elguero
J
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014320:Triphenylmethyl Compounds / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D004396:Coloring Agents; D014320:Triphenylmethyl Compounds; D014344:Trypanocidal Agents; D004247:DNA; D013936:Thymidine