In vitro leishmanicidal activity of naturally occurring chalcones.
A variety of chalcones have been shown to exhibit activity against Leishmania parasites. In contrast to synthetic or semisynthetic chalcones, only a few plant-derived compounds have been investigated. To provide a scientific rational for the antiprotozoal potency of plants used in ethnomedicine and containing chalcones, and in the search for new antiprotozoal drugs, we have carried out a primary screening for in vitro leishmanicidal activity of 20 chalcones isolated from plants. The compounds were tested against extracellular promastigotes of Leishmania donovani, L. infantum, L. enrietii and L. major, and against intracellular amastigote L. donovani residing within murine macrophages. Against the extracellular Leishmania (L. donovani), most compounds were active with EC(50) values between 0.07 and 2.01 microg/mL. Some of these chalcones, 2',4'-dihydroxy-4-methoxychalcone, 2'-hydroxy-3,4-dimethoxychalcone and 2-hydroxy-4,4'-dimethoxychalcone also significantly inhibited the intracellular survival of L. donovani parasites with EC(50) values between 0.39 and 0.41 microg/mL. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, all compounds with antileishmanial activities also proved to be cytotoxic to varying extents (EC(50) 0.19-2.06 microg/mL). Correlations between molecular structures and antileishmanial activity are discussed in detail. Specific compounds are illustrated with emphasis on their mode of action and potential for the development of selective antiprotozoal agents.
Freie Universität Berlin, Institute of Pharmacy, Kelchstrasse 31, D-12169 Berlin, Germany. kayser@zedat.fu-berlin.de
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D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D002599:Chalcone