BACKGROUNDIn a screen of extracts from plants and fungi to detect antileishmanial
activity, we found that the ethyl acetate extract of the fungus
Nectria pseudotrichia, isolated from the tree
Caesalpinia echinata (Brazilwood), is a promising
source of bioactive compounds.OBJECTIVESThe aims of this study were to isolate and determine the chemical structures
of the compounds responsible for the antileishmanial activity of the organic
extract from N. pseudotrichia.METHODSCompounds were isolated by chromatographic fractionation using
semi-preparative high-performance liquid chromatography, and their chemical
structures were determined by analytical and spectral data and by comparison
with published data. The antileishmanial activity of the isolated compounds
was evaluated in intracellular amastigote forms of Leishmania
(Viannia) braziliensis expressing firefly luciferase as
reporter gene, and cytotoxicity was determined in Vero and THP-1 mammalian
cell lines by MTT assay.FINDINGSFractionation of the extract yielded seven compounds: 10-acetyl trichoderonic
acid A (1), 6′-acetoxy-piliformic acid (2), 5′,6′-dehydropiliformic acid
(3), piliformic acid (4), hydroheptelidic acid (5), xylaric acid D (6), and
cytochalasin D (7). Compounds 1, 2 and 3 are reported here for the first
time. Compounds 1, 2, and 5 were more active, with IC50 values of
21.4, 28.3, and 24.8 µM, respectively, and showed low toxicity to Vero and
THP-1 cells.MAIN CONCLUSIONS
N. pseudotrichia produces secondary metabolites that are
more toxic to intracellular amastigote forms of L. (V.)
braziliensis than to mammalian cells.
Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi. Only two drugs are available, with the drawback of low rate of cure in the chronic phase of the disease and undesirable side effects. These facts highlight the need to find new compounds for Chagas disease chemotherapy. We describe the isolation and identification of an inseparable mixture of two new trixikingolides from Trixis vauthieri, a plant from family Asteraceae, which present outstanding in vitro trypanocidal activity, with IC 50 value of 0.053 µM against the intracellular trypomastigotes and amastigotes forms of T. cruzi infecting L929 cells. The IC 50 of the mixture against the host cells is 68 times higher and about 70 times more potent than benznidazole, the reference drug used as control at the experiments. The next step, which depends on obtaining larger quantities of the mixture, is to test it on mice infected with T. cruzi.
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