Two new prenylated indole alkaloids, namely, dihydrocarneamide A (1) and iso-notoamide B (2), were isolated from the marine-derived endophytic fungus Paecilomyces variotii EN-291. The structures of these metabolites were determined based on comprehensive spectral analysis, together with chiral HPLC analysis of the acidic hydrolysates. Unlike other prenylated indole alkaloids such as asperparalines, notoamides, and versicolamides, compounds 1 and 2 are the rare examples of C-5 prenylation, forming the fused dimethyldihydropyran ring at C-5 and C-6 of the indole ring. The cytotoxic activity of the isolated compounds was evaluated. (C) 2014 Bin-Gui Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.