LICOCHALCONE A, A NOVEL ANTIPARASITIC AGENT WITH POTENT ACTIVITY AGAINST HUMAN PATHOGENIC PROTOZOAN SPECIES OF LEISHMANIA

Licochalcone A, an oxygenated chalcone isolated from the roots of Chin ese licorice plant, inhibited the growth of both Leishmania major and Leishmania donovani promastigotes and amastigotes. The structure of th e licochalcone A was established by mass and nuclear magnetic resonanc e spectroscopies and by synthesis, and its purity was verified by high -pressure liquid chromatography. The 50% inhibition of growth of logar ithmic- and stationary-phase promastigotes of L. major, as measured by [H-3]thymidine uptake, were 4 and 2.5 mu g/ml, respectively. The grow th of L. major promastigotes was totally inhibited after a 20-h incuba tion period with licochalcone A at 5 mu g/ml. At a concentration of 0. 5 mu g/ml, licochalcone A markedly reduced the infection rate of human peripheral blood monocyte-derived macrophages and U937 cells with L. major promastigotes and exhibited a strong intracellular killing of th e parasite. These data show that intracellular Leishmania amastigotes are more susceptible than promastigotes to licochalcone A. Results of studies on the site of action of licochalcone A indicate that the targ et organelle appears to be the parasite mitochondria. These findings d emonstrate that licochalcone A in concentrations that are nontoxic to host cells exhibits a strong antileishmanial activity and that appropr iate substituted chalcones might be a new class of antileishmanial dru gs.