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: Alexander Deterding, Fiona A Dungey, Katy-Anne Thompson, Dietmar Steverding
• Journal: Acta tropica (Acta Trop) Vol. 93 Issue 3 Pg. 311-6 (Mar 2005) ISSN: 0001-706X [Print] Netherlands
• PMID: 15715983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiprotozoal Agents
• Topoisomerase I Inhibitors

Topics

• Animals
• Antiprotozoal Agents (therapeutic use)
• HL-60 Cells
• Humans
• Microbial Sensitivity Tests
• Topoisomerase I Inhibitors
• Trypanosoma brucei brucei (drug effects)
• Trypanosomiasis, African (drug therapy)