Secondary Metabolites from the Fungus Dictyosporium sp. and Their MALT1 Inhibitory Activities

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2019-01, Vol.82 (1), p.154-162
• Main Authors: Tran, Trong D, Wilson, Brice A. P, Henrich, Curtis J, Staudt, Louis M, Krumpe, Lauren R. H, Smith, Emily A, King, Jarrod, Wendt, Karen L, Stchigel, Alberto M, Miller, Andrew N, Cichewicz, Robert H, O’Keefe, Barry R, Gustafson, Kirk R
• Format: Article
• Language: English
• Subjects: Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Fungi - metabolism; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein - antagonists & inhibitors
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.8b00871

Bioassay-guided separation of an extract from a Dictyosporium sp. isolate led to the identification of six new compounds, 1–6, together with five known compounds, 7–11. The structures of the new compounds were primarily established by extensive 1D and 2D NMR experiments. The absolute configurations of compounds 3–6 were determined by comparison of their experimental electronic circular dichroism (ECD) spectra with DFT quantum mechanical calculated ECD spectra. Compounds 3–5 possess novel structural scaffolds, and biochemical studies revealed that oxepinochromenones 1 and 7 inhibited the activity of MALT1 protease.