Three new bis-3-alkylpyridine alkaloids, pyrinodemins G-I (1-3), were isolated from an Okinawan marine sponge Amphimedon sp. and the structures of 1-3 were elucidated on the basis of spectroscopic data. Pyrinodemins G-I (1-3) were novel bis-3-alkylpyridine alkaloids possessing an N-methoxy amide moiety, an alpha,beta-unsaturated 3,5-disubstituted gamma-lactone moiety, and a 2,3-di-substituted acrolein at a junction of two 3-alkylpyridines, respectively. Pyrinodemins G (1) and H (2) showed cytotoxicity against P388 murine leukemia cells. (C) 2012 Elsevier Ltd. All rights reserved.