title: Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi.
abstract: 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.
authors.affiliation: BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Momodou
authors.initials: M
authors.lastname: Jobe
authors.forename: Charles
authors.initials: C
authors.lastname: Anwuzia-Iwegbu
authors.forename: Ama
authors.initials: A
authors.lastname: Banful
authors.forename: Emma
authors.initials: E
authors.lastname: Bosier
authors.forename: Mubeen
authors.initials: M
authors.lastname: Iqbal
authors.forename: Kelly
authors.initials: K
authors.lastname: Jones
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Lecutier
authors.forename: Kasimir
authors.initials: K
authors.lastname: Lepper
authors.forename: Matt
authors.initials: M
authors.lastname: Redmond
authors.forename: Andrew
authors.initials: A
authors.lastname: Ross-Parker
authors.forename: Emily
authors.initials: E
authors.lastname: Ward
authors.forename: Paul
authors.initials: P
authors.lastname: Wernham
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Whidden
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Tyler
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
mesh_terms: D005434:Flow Cytometry; D015255:Idarubicin / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D059003:Topoisomerase Inhibitors / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development; D057509:Trypanosoma rangeli / Q000187:drug effects* / Q000254:growth & development
chemical_list: D059003:Topoisomerase Inhibitors; D014344:Trypanocidal Agents; D015255:Idarubicin