Antimicrobial Agents and Chemotherapy · 1992 · 34 citations · 11 references
MedicineMedicinal ChemistryPharmacologyAntimicrobial PharmacologyChemotherapyEnzymologyAntiparasitic AgentsCytotoxic ChemotherapyEnzyme InhibitionProtozoal InfectionsProtozoan PathogenesisTopoisomerase InhibitorsAntileishmanial ChemotherapyAntileishmanial TreatmentCell LysisDna Topoisomerase Ii InhibitionFlagellar MotilityLeishmaniasis PathogenesisTopoisomerase Ii InhibitorsTreatment Of Leishmaniasis
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.
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DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II.
Thomas C. Rowe, Grace L. Chen, Y H Hsiang et al. · PubMed · 1986 · 236 citations