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PAGES: 102-110 DOI: 10.1590/0074-02760170217 Full paper
Leishmanicidal compounds of Nectria pseudotrichia, an endophytic fungus isolated from the plant Caesalpinia echinata (Brazilwood)

Betania Barros Cota1+, Luiza Guimarães Tunes2, Daniela Nabak Bueno Maia1, Jonas Pereira Ramos3, Djalma Menezes de Oliveira4, Markus Kohlhoff1, Tânia Maria de Almeida Alves1, Elaine Maria Souza-Fagundes3, Fernanda Fraga Campos5, Carlos Leomar Zani1

1Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Laboratório de Química de Produtos Naturais Bioativos, Belo Horizonte, MG, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Laboratório de Genômica Funcional e Proteômica de Leishmania spp. e Trypanosoma cruzi, Belo Horizonte, MG, Brasil
3Universidade Federal de Minas Gerais, Departamento de Fisiologia e Biofísica, Belo Horizonte, MG, Brasil
4Universidade Estadual do Sudoeste da Bahia, Departamento de Química, Jequié, BA, Brasil
5Universidade Federal dos Vales do Jequitinhonha e Mucuri, Departamento de Ciências Biológicas e da Saúde, Diamantina, MG, Brasil


BACKGROUND In 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.

OBJECTIVES The 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.

METHODS Compounds 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.

FINDINGS Fractionation 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.

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Financial support: CNPq, FAPEMIG, PDTIS-FIOCRUZ (RPT-10A and RPT13-A).
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Received 1 June 2017
Accepted 22 August 2017