In vitro leishmanicidal activity of naturally occurring chalcones

A variety of chalcones have been shown to exhibit activity against Leishman ia parasites, In contrast to synthetic or semisynthetic chalcones, only a f ew 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 hav e carried out a primary screening for in vitro leishmanicidal activity of 2 0 chalcones isolated from plants. The compounds were tested against extrace llular promastigotes of Leishmania donovani, L. infantum, L. enrietii and L . major, and against intracellular amastigote L. donovani residing within m urine macrophages, Against the extracellular Leishmania (L. donovani), most compounds were active with EC50 values between 0.07 and 2.01 mug/mL. Some of these chalcones, 2',4'-dihydroxy-4-methosychalcone, 2'-hydroxy-3,4-dimet hoxychalcone and 2-hydroxy-4,4'-dimethoxychalcone also significantly inhibi ted the intracellular survival of L, donorvani parasites with EC50 values b etween 0.39 and 0.41 mug/mL. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, all compounds with antileish manial activities also proved to be cytotoxic to varying extents (EC50 0.19 -2.06 mug/mL). Correlations between molecular structures and antileishmania l activity are discussed in detail, Specific compounds are illustrated with emphasis on their mode of action and potential for the development of sele ctive antiprotozoal agents. Copyright (C) 2001 John Wiley & Sons, Ltd.