Leishmanicidal compounds of Nectria pseudotrichia, an endophytic fungus isolated from the plant Caesalpinia echinata (Brazilwood)

Abstract

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.

Leishmanicidal, cytotoxic, antimicrobial and enzymatic activities of Diaporthe species, a mangrove-isolated endophytic fungus

“…Therefore, contributing studies that may lead to the discovery of a compound or compounds with anti-leishmaniasis activity is of great importance for the control of these diseases. Similar works tested endophytic fungi isolated from plants from different Brazilian biomes, and they obtained leishmanicides that exhibited promise against other species of Leishmania that cause integumentary leishmaniasis, which is less deadly than visceral leishmaniasis (VL) (Marinho et al, 2005;Campos et al, 2008;Rosa et al, 2010;Brissow et al, 2017;Cota et al, 2018). Little is known about the anti-leishmaniasis activity of these isolates against the species that cause VL (Leishmania donovani and L. infantum chagasi).…”

“…However, this leishmaniasis is the least severe and lethal. A number of studies have demonstrated activities against this type of leishmaniasis (Santiago et al, 2011;Cota et al, 2018). To date, there have been no studies investigating the role played by related endophytic fungi from mangroves in producing secondary metabolites with leishmanicidal activity against L. infantum chagasi.…”

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“…Endo-phytic fungi are the major contributor to most of the natural products produced by endophytic microorganisms 9 . The natural products produced by endophytic fungi have potential applications in the development of antimicrobial, antiviral 10 , antileishmanial 11 , anti-oxidant, anticancer, antiparasitic, and bio-control agents 12 .…”

Anti-leishmanial and Anti-inflammatory Agents from Endophytes: A Review

“…These compounds active in the micromolar range are also small molecules, ideal for further optimization through medicinal chemistry. Recently, in a preliminary screening to search potential antileishmanial compounds, Cota et al [34] identified ethyl acetate extract of the fungus Nectria pseudotrichia, an endophyte of Caesalpinia echinata as promising against Leishmania braziliensis. The fractionation led to seven compounds including 10-acetyl trichoderonic acid A (21), 6′-acetoxy-piliformic acid (22), 5′,6′-dehydropiliformic acid (23), piliformic acid (24), hydroheptelidic acid (25), xylaric acid D (26), and cytochalasin D (27) [36].…”