title: Anti-trypanosomal activities of DNA topoisomerase inhibitors.
abstract: Only four drugs are available for chemotherapy of human African sleeping sickness with undesirable toxic side effects. The development of new anti-trypanosomal drugs is, therefore, urgently required. In this study, 15 DNA topoisomerase inhibitors, including approved anti-cancer drugs, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL-60 cells. All compounds exhibited anti-trypanosomal activity, with ED50 values ranging between 3 nM and 30 microM, and MIC values between 100 nM and >100 microM. The trypanocidal activities of the most effective DNA topoisomerase inhibitors, aclarubicin, doxorubicin and mitoxantrone, were comparable with those of commercial anti-trypanosomal drugs. These data support the use of DNA topoisomerase inhibitors as lead compounds for anti-trypanosomal drug development.
authors.affiliation: School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Deterding
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Dungey
authors.forename: Katy-Anne
authors.initials: KA
authors.lastname: Thompson
authors.forename: Dietmar
authors.initials: D
authors.lastname: Steverding
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D018922:HL-60 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D059004:Topoisomerase I Inhibitors; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D000981:Antiprotozoal Agents; D059004:Topoisomerase I Inhibitors