This is the first report on aurones as a new class of natural products with leishmanicidal activity. A series of aurones with drug-potential for Leishmania infections was identified in vitro using both a direct cytotoxicity test against extracellular promastigotes of Leishmania donovani, L. infantum, L. enriettii, and L. major, and a test against intracellular amastigote L. donovani residing within murine macrophages. The compounds proved to be active at concentrations in the microgram range between 0.4 and 5.0 microg/ml. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, all compounds showed only moderate cytotoxicity (EC50 2.32-25.0 microg/ml).