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

Submitted by Nuzia Santos ([email protected]) on 2018-03-07T17:32:29Z No. of bitstreams: 1 Leishmanicidal compounds of Nectria pseudotrichia.pdf: 404788 bytes, checksum: d3f619503129576e6ba497bfcd75b025 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-03-07T17:38:29Z (GMT) No. of bitstreams: 1 Leishmanicidal compounds of Nectria pseudotrichia.pdf: 404788 bytes, checksum: d3f619503129576e6ba497bfcd75b025 (MD5)Made available in DSpace on 2018-03-07T17:38:29Z (GMT). No. of bitstreams: 1 Leishmanicidal compounds of Nectria pseudotrichia.pdf: 404788 bytes, checksum: d3f619503129576e6ba497bfcd75b025 (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Química de Produtos Naturais Bioativos. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Genômica Funcional e Proteômica de Leishmania spp. e Trypanosoma cruzi. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Química de Produtos Naturais Bioativos. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrasilUniversidade Estadual do Sudoeste da Bahia. Departamento de Química. Jequié, BA, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Química de Produtos Naturais Bioativos. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Química de Produtos Naturais Bioativos. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrasilUniversidade Federal dos Vales do Jequitinhonha e Mucuri. Departamento de Ciências Biológicas e da Saúde. Diamantina, MG, BrasilFundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Química de Produtos Naturais Bioativos. Belo Horizonte, MG, BrasilBACKGROUND: 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

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

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