Speradines B-E, Four Novel Tetracyclic Oxindole Alkaloids from the Marine-Derived Fungus Aspergillus oryzae

Four novel tetracyclic oxindole alkaloids, namely, speradines B (1), C(2), D (3), and E (4) were isolated from the marine-derived fungus Aspergillus oryzae.The structures of these compounds without the absolute configurations were elucidated through 1D and 2D nuclear magnetic resonance and high-resolution mass spectrometric analyses.Among these compounds, 1 and 4 showed weak cytotoxic effects on the HeLa cell line.Indole-terpenes are fungal and bacterial secondary metabolites with unique biological activities such as inhibitory activity of calcium-activated potassium channels, 1 antitumor activity, 2 tremorgenic activity, 3 potent and selective progesterone receptor agonistic activity, 4 and anti-MRSA activity. 5Cyclopiazonic acid (CPA)-type alkaloids are one important group of indole-terpenes, and they usually contain three structural units: an indole, a dimethylallyl (DMA), and two acetic acids.Only six analogous natural products have been reported to date, including α-cyclopiazonic acid, 6 iso-α-cyclopiazonic acid, 7 β-cyclopiazonic acid, 6 α-acetyl-γ-(β-indolyl)methyl-tetramic acid, 8 speradine A, 9 and 3-hydroxyl speradine A. 10 In our search for novel anticancer compounds, 11 a strain of Aspergillus oryzae showed significant cytotoxic activity.