Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi

• Published in: Memórias do Instituto Oswaldo Cruz 2012-11, Vol.107 (7), p.946-950
• Main Authors: Jobe, Momodou, Anwuzia-Iwegbu, Charles, Banful, Ama, Bosier, Emma, Iqbal, Mubeen, Jones, Kelly, Lecutier, Suzanne J, Lepper, Kasimir, Redmond, Matt, Ross-Parker, Andrew, Ward, Emily, Wernham, Paul, Whidden, Eleanor M, Tyler, Kevin M, Steverding, Dietmar
• Format: Article
• Language: English
• Subjects: Chagas disease; chemotherapy; DNA topoisomerase inhibitors; drug screening; Flow Cytometry; Idarubicin - pharmacology; Parasitic Sensitivity Tests; PARASITOLOGY; Topoisomerase Inhibitors - pharmacology; TROPICAL MEDICINE; Trypanocidal Agents - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - growth & development; Trypanosoma rangeli; Trypanosoma rangeli - drug effects; Trypanosoma rangeli - growth & development
• ISSN: 0074-0276; 1678-8060; 1678-8060; 0074-0276
• DOI: 10.1590/S0074-02762012000700018

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI(50)) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI(50) value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.