Dothiorelone derivatives from an endophyte Diaporthe pseudomangiferaea inhibit the activation of human lung fibroblasts MRC-5 cells

Abstract

Nine new compounds (1-6 and 16-18) and nine known compounds (7-15) were isolated from Diaporthe pseudomangiferaea, an endophytic fungus obtained from the leaves of the toxic Chinese folk medicine Tylophora ouata. Their structures were elucidated by NMR spectroscopy and MS spectrometry analyses. The absolute configurations were established according to the specific rotation or electron circular dichroism method. Compounds 1, 4, 9, 11, 14 and 15 inhibited the TFG-β induced activation of human lung fibroblasts MRC-5 cells by 17.4%, 59.2%, 62.9%, 41.1%, 32.9% and 52.1% at 10 μM, respectively, while positive control pirfenidone showed 53.2% inhibition rate at 1 mM. The MTT assay showed that compounds 13 and 14 displayed cytotoxicity against BGC-823 cells, with IC₅₀ values of 8.1 and 4.4 μM, respectively.

Keywords: Anti-fibrosis; Dothiorelones; Endophytic fungi; TFG-β.