Selective Effect of 2′,6′-Dihydroxy-4′-Methoxychalcone Isolated fromPiper aduncumonLeishmania amazonensis

Abstract

2′,6′-Dihydroxy-4′-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 μg/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 metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 μg/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 μg of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

Activity of the julocrotine, a glutarimide alkaloid from Croton pullei var. glabrior, on Leishmania (L.) amazonensis

“…The ultrastructural changes shown in the promastigotes of L. (L.) amazonensis in this report are similar to those observed by other authors (Vannier-Santos et al 1995;Torres-Santos et al 1999;Delorenzi et al 2001;Rodrigues et al 2002;Rosa et al 2003;Brenzan et al 2007;Rodrigues et al 2008). Untreated L. amazonensis promastigotes showed typical morphology.…”

Ultrastructural alterations induced by the neolignan dihydrobenzofuranic eupomatenoid-5 on epimastigote and amastigote forms of Trypanosoma cruzi

“…Recently, Braga et al (2004) showed that the presence of ergosterol and analogs is essential for the maintenance of normal structural organization, especially of the inner mitochondrial membrane, in these protozoa. Several studies have also shown ultrastructural alterations in Leishmania amazonensis treated with synthetic or natural compounds (Torres-Santos et al 1999;Rodrigues et al 2002).…”

Flavour compounds of Greek cotton honey

“…19 Pinostrobin chalcone has been isolated from Piper aduncum and exhibits significant activity against Leishmania amazonensis. 20 It has also been reported as a constituent of Egyptian 21 and Brazilian 22 propolis. Scopoletin and scoparone are simple coumarins that have been isolated from various botanical species.…”