Three new prenylated indole alkaloids, including two -carbolines, penipalines A and B (1 and 2, resp.), and one indole carbaldehyde derivative, penipaline C (3), as well as two known indole derived analogs, 4 and 5, were isolated from the deep-sea-sediment derived fungus Penicillium paneum SD-44 cultured in a 500-l bioreactor. The structures of the new compounds were determined on the basis of 1D- and 2D-NMR spectroscopy, as well as by high-resolution mass spectrometry. The new compounds 2 and 3 showed potent cytotoxic activities against A-549 and HCT-116 cell lines.