Asperindoles A⁻D and a p -Terphenyl Derivative from the Ascidian-Derived Fungus Aspergillus sp. KMM 4676.

Four new indole-diterpene alkaloids asperindoles A⁻D ( 1 ⁻ 4 ) and the known p -terphenyl derivative 3″-hydroxyterphenyllin ( 5 ) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1 ⁻ 5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1 ⁻ 4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate cancer cells, and induces apoptosis in these cells at low-micromolar concentrations.