Cytotoxicity of acridine compounds for Leishmania promastigotes in vitro.
The effect of mammalian and bacterial topoisomerase II inhibitors on Leishmania promastigotes was studied in vitro. Parasites were incubated with drugs, and cytotoxicity was assessed on the basis of the loss of flagellar motility and cell lysis after 48 h. 9-Aminoacridines, which are structurally related to the known antileishmanial compounds quinacrine and chlorpromazine, showed activity against the parasite at concentrations in the range of 10 to 20 microM. Adriamycin showed far less activity, while etoposide and several quinolones were inactive at 100-microM concentrations. These results demonstrate that a particular structural class of compounds is cytotoxic to Leishmania species. The unique structure-activity relationship discovered suggests that leishmanial topoisomerase II could be a useful target for chemotherapy.
Werbovetz
K A
KA
Department of Chemistry, University of Virginia, Charlottesville 22901.
Lehnert
E K
EK
Macdonald
T L
TL
Pearson
R D
RD
D000166:Acridines / Q000494:pharmacology*; D000818:Animals; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000166:Acridines; D059005:Topoisomerase II Inhibitors