We present the isolation and characterization of seven novel (natural) pyrroloiminoquinones, the makaluvamines A-F (1-6), makaluvone (7), and the known compounds discorhabdin A (8) and damirone B (9) from the Fijian sponge Zyzzya cf. marsailis. The makaluvamines exhibit potent in vitro cytotoxicity toward the human colon tumor cell-line HCT 116, show differential toxicity toward the topoisomerase I1 sensitive CHO cell-line xrs-6, and inhibit topoisomerase I1 in vitro. This activity may be mediated by intercalation into DNA and single-stranded breakage. Makaluvamine A and C exhibited in vivo antitumor activity against the human ovarian carcinoma Ovcar3 implanted in athymic mice. The makaluvamines suggest a plausible interrelationship between the batzelline/isobatzelline and discorhabdin/prianosin classes of compounds. Marine sponges and ascidians have proven to be a valuable source of a variety of biologically active secondary metabolites;2 recently, a series of publications described a new class of highly cytotoxic pyrroloiminoquinones based on a pyrrolo(4,3,2-de)- quinoline skeleton: batzellines and isobatzellines, isolated from the Caribbean sponge Batzella SP.,~ damirones, isolated from the Palauan sponge Damiria SP.,~ discorhabdins, isolated from New Zealand sponges of the genus Lutrunc~lia,~ prianosins, isolated from the Okinawan sponge Prianos melanos,6 and most recently, wakayin, isolated from the Fijian ascidian Clavelina sp.' As a part of our continuing search for potential antineoplastic agents from marine sources, we isolated makaluvamines A-F, makaluvone, and the known compounds damirone B and disco- rhabdin A from the Fijian sponge Zyrzya cf. marsailis.8 We report here the structure determination of the new compounds and preliminary evidence for the ability of this class of metabolites to inhibit the function of mammalian topoisomerase 119 and to inhibit the growth of human ovarian tumor in an athymic mouse model.