| Autor: |
Cota BB; Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil., Tunes LG; Laboratório de Genômica Funcional e Proteômica de Leishmania spp. e Trypanosoma cruzi, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil., Maia DNB; Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil., Ramos JP; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil., Oliveira DM; Departamento de Química, Universidade Estadual do Sudoeste da Bahia, Jequié, BA, Brasil., Kohlhoff M; Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil., Alves TMA; Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil., Souza-Fagundes EM; Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil., Campos FF; Departamento de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, MG, Brasil., Zani CL; Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, MG, Brasil. |
| Abstrakt: |
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. |
