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

Abstract

Four new indole-diterpene alkaloids asperindoles A⁻D (<b>1</b>⁻<b>4</b>) and the known <i>p</i>-terphenyl derivative 3&Prime;-hydroxyterphenyllin (<b>5</b>) were isolated from the marine-derived strain of the fungus <i>Aspergillus</i> sp., associated with an unidentified colonial ascidian. The structures of <b>1</b>⁻<b>5</b> were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of <b>1</b>⁻<b>4</b> 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.