Ec. Torres-santos et al., Selective effect of 2 ',6 '-dihydroxy-4 '-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis, ANTIM AG CH, 43(5), 1999, pp. 1234-1241
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.