Selective effect of 2 ',6 '-dihydroxy-4 '-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis

2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichlorometh ane extract of Piper aduncum inflorescences. DMC showed significant activit y in vitro against promastigotes and intracellular amastigotes of Leishmani a amazonensis, with 50% effective doses of 0.5 and 24 mu g/ml, respectively . Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolis m of macrophages, since the production of nitric Oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rath er than increased with DMC. The phagocytic activity of macrophages was func tioning normally even with DMC concentrations as high as 80 mu g/ml, as see n by electron microscopy and by the uptake of fluorescein isothiocyanate-la beled beads. Ultrastructural studies also showed that in the presence of DM C the mitochondria of promastigotes were enlarged and disorganized; Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 mu g of DMC/ml. These observations sug gest that DMC is selectively toxic to the parasites. Its simple structure m ay well enable it to serve as a new lead compound for the synthesis of nove l antileishmanial drugs.